Interleukin-1 Alpha Production Research Articles

Airway Exposure to Staphylococcus Aureus Particles Promotes Development of Antigen-Specific Th2-Type Immunity to Inhaled Antigens through Production of Interleukin-1 Alpha (IL-1 alpha)

Airway Exposure to Staphylococcus Aureus Particles Promotes Development of Antigen-Specific Th2-Type Immunity to Inhaled Antigens through Production of Interleukin-1 Alpha (IL-1 alpha)

Senescence in chronic allograft nephropathy.

Despite increasing numbers of patients on dialysis, the numbers of renal transplants performed yearly have remained relatively static. During the last 50 years, there have been many advances in the pharmacology of prevention of organ rejection. However, most patients will suffer from a slow but steady decline in renal function leading to graft loss. The most common cause of long-term graft loss is chronic allograft nephropathy (CAN). Therefore, elucidating and understanding the mechanisms involved in CAN is crucial for achieving better posttransplant outcomes. It is thought that the development of epithelial to mesenchymal transition (EMT) in proximal tubules is one of the first steps towards CAN, and has been shown to be a result of cellular senescence. Cells undergoing senescence acquire a senescence associated secretory phenotype (SASP) leading to the production of interleukin-1 alpha (IL-1α), which has been implicated in several degenerative and inflammatory processes including renal disease. A central mediator in SASP activation is the production of reactive oxygen species (ROS), which are produced in response to numerous physiological and pathological stimuli. This review explores the connection between SASP and the development of EMT/CAN in an effort to suggest future directions for research leading to improved long-term graft outcomes.

Immunomodulatory and Antigenotoxic Properties of Bacillus amyloliquefaciens KU801

The Bacillus KU801 strain, due to its potential in the field of probiotics for animal use, was isolated from chicken feces. Strain KU801 was identified as Bacillus amyloliquefaciens KU801 based on the results of 16S rRNA sequencing. Vegetative and spore cells of B. amyloliquefaciens KU801 were resistant to artificial gastric juice and artificial bile acid. B. amyloliquefaciens KU801 was found to inhibit the production of nitric oxide (NO) and increase the production of Interleukin-1 alpha (IL-1). DNA damage induced by N-methyl-Ntion of ninitroso-guanidine (MNNG) was significantly inhibited, in a dose dependent manner, by preincubating MNNG together with B. amyloliquefaciens KU801. These results demonstrate the potential use of B. amyloliquefaciens KU801 as a feed additive.

Virus Distribution and Role of Thymic Macrophages During Experimental Infection With Noncytopathogenic Bovine Viral Diarrhea Virus Type 1

Thymic depletion, presence of viral antigen, and changes in distribution and cytokine production of thymic macrophages were investigated in calves experimentally infected with a noncytopathogenic bovine viral diarrhea virus type (BVDV) 1 strain. Ten clinically healthy colostrum-deprived calves were used. Eight calves were inoculated with the virus and two were used as uninfected controls. Calves were sedated and euthanized in batches between 3 and 14 days postinoculation. At necropsy, thymus samples were collected for structural, immunohistochemical, and ultrastructural study and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling). From 6 days postinoculation, the thymic cortex was multifocally depleted with increased frequency of pyknosis and karyorrhexis, suggestive of apoptosis and confirmed by the TUNEL technique. Although the onset of lymphoid depletion was coincident with the detection of viral antigen by immunohistochemistry, the number of infected lymphocytes was very low through the experiment. There was an increase in number of macrophages in cortex and medulla, accompanied by ultrastructural changes indicative of phagocyte activation, and a decrease in cells expressing tumor necrosis factor-alpha (TNF-α) and IL-1α. These results suggest that the increase in number of these cells could be related to phagocytosis of cell debris and apoptotic lymphocytes. Furthermore, the results imply that, in contrast to the situation with classical swine fever virus, the lymphocyte apoptosis resulting from bovine viral diarrhea virus infection is not mediated by TNF-α or interleukin-1 alpha (IL-1α) production by virus-infected macrophages. This is the first study that describes this decrease in the number of thymic cells expressing TNF-α and IL-1α in cattle experimentally infected with bovine viral diarrhea virus type 1.

Effects of endostatin production on oncogenicity and metastatic activity of HPV16-transformed mouse cells: Role of interleukin 1α

Two mouse HPV16-transformed cell lines, viz. MK16 cells, which induce metastasizing tumors, and TC-1 cells, which induce non-metastasizing tumors were transduced with the gene for mouse endostatin. Two clones constitutively expressing endostatin were isolated from each of them. They were denoted ME3 and ME9, and TE2 and TE5, respectively. When inoculated into mice, ME3 cells were non-oncogenic. Nearly all mice inoculated with ME9 cells developed tumors, but considerably later than did the parental MK16 cells and metastasis formation was strongly reduced in these animals. On the other hand, TE2 and TE5 cells displayed oncogenic potential similar to that of the parental cells. To provide more information on these different effects of endostatin production, cell lysates of all six lines studied were tested for the content of 25 factors known to be involved in angiogenesis. The parental MK16 cells differed from the parental TC-1 cells and also from all endostatin producing sublines by a markedly higher production of interleukin 1alpha (IL-1alpha) and, to a lesser extent, by a higher production of several other factors tested. Additional experiments indicated that the suppression of the production of IL-1alpha by the parental MK16 caused by endostatin was due to an autocrine mechanism.

Function of oleic acid on epidermal barrier and calcium influx into keratinocytes is associated withN-methyl d-aspartate-type glutamate receptors

Unsaturated fatty acids from sebum affect calcium dynamics in epidermal keratinocytes, disrupt the barrier function and induce abnormal keratinization. However, the mechanisms of these effects have not been clarified. To investigate the function of unsaturated fatty acids in epidermis. Antagonists of calcium channel receptors were applied to mouse skin together with oleic acid. Measurements were made of transepidermal water loss (TEWL), and hyperproliferation was assessed. The effects of the antagonists on calcium influx into cultured normal human keratinocytes and on cytokine production were also evaluated. N-methyl-d-aspartate (NMDA) receptor antagonists such as MK801 and D-AP5 specifically inhibited the increase in TEWL caused by oleic acid, and suppressed keratinocyte hyperproliferation. These compounds also inhibited the increase in the intracellular concentration of calcium ions induced by oleic acid. MK801 suppressed the production of interleukin-1alpha by keratinocytes induced by oleic acid. Unsaturated fatty acids such as oleic acid might function via NMDA receptors.

Production of inflammatory cytokines by peripheral blood monocytes in chronic alcoholism: Relationship with ethanol intake and liver disease

Controversial results have been reported about the effects of alcoholism on the functionality of monocytes. In the present study we analyze the effects of chronic alcoholism on the intracellular production of inflammatory cytokines by peripheral blood (PB) monocytes. Spontaneous and in vitro-stimulated production of interleukin (IL) 1alpha (TNFalpha) by PB monocytes was analyzed at the single level by flow cytometry in chronic alcoholics without liver disease and active ethanol (EtOH) intake (AWLD group), as well as in patients with alcohol liver cirrhosis (ALC group), who were either actively drinking (ALCET group) or with alcohol withdrawal (ALCAW group). A significantly increased spontaneous production of IL1beta, IL6, IL12, and TNFalpha was observed on PB monocytes among AWLD individuals. Conversely, circulating monocytes form ALCET patients showed an abnormally low spontaneous and stimulated production of inflammatory cytokines. No significant changes were observed in ALCAW group as regards production of IL1beta, IL6, IL12, and TNFalpha. Our results show an altered pattern of production of inflammatory cytokines in PB monocytes from chronic alcoholic patients, the exact abnormalities observed depending on both the status of EtOH intake and the existence of alcoholic liver disease.

Lipopolysaccharide enhances in vivo interleukin‐2 production and proliferation by naive antigen‐specific CD4 T cells via a Toll‐like receptor 4‐dependent mechanism

Microbial adjuvants are essential for the development of T-cell-dependent antibody production, recall T-cell proliferation and interferon-gamma production following immunization with protein antigens. Using an adoptive transfer approach, we showed that the adjuvant lipopolysaccharide enhanced the frequency of cells producing interleukin-2, enhanced clonal expansion by antigen-specific CD4 T cells and increased CD86 and interleukin-1alpha production by antigen-presenting cells. All of these effects were dependent on Toll-like receptor-4 (TLR4) expression by cells other than the antigen-specific CD4 T cells. The ability of lipopolysaccharides to increase the number of antigen-specific CD4 T cells that survive after immunization probably explains the previous finding that antigen-specific proliferation by T cells from normal mice depends on previous exposure to antigen and adjuvant.

Corticotropin-Releasing Hormone Skin Signaling is Receptor-Mediated and is Predominant in the Sebaceous Glands

There is increasing evidence that the sebaceous gland expresses receptors for several neuropeptides and is involved in responses to stress. Among them, corticotropin-releasing hormone (CRH) was currently found to be produced also in the skin. In this study, the distribution of CRH, CRH receptors 1 and 2 (CRH-R1 and CRH-R2), and CRH binding protein (CRH-BP) in cultured human (SZ95) sebocytes was further characterized. Moreover, the effects of CRH and CRH-like peptides on proliferation and inflammatory signaling of CRH receptor-expressing SZ95 sebocytes IN VITRO were investigated. Urocortin (Uct), urotensin and sauvagine are recently described members of the family of structurally related CRH-like peptides, whereas Uct shares a 45% homology with CRH. CRH and Uct inhibited SZ95 sebocyte proliferation with CRH also stimulating interleukin-6 (IL-6) and interleukin-8 (IL-8) release from SZ95 sebocytes. However, CRH had no effect on interleukin-1alpha and interleukin-1beta production in these cells. alpha-Helical-CRF, a CRH antagonistic peptide, annulled the CRH effect on SZ95 sebocyte proliferation and interleukin secretion, while the non-peptidic CRH-R1 selective antagonist antalarmin inhibited the increased production of neutral lipids caused by CRH. In conclusion, CRH, and to a lesser extent Uct, may be involved in signaling of stress pathophysiology in the skin. However, further investigations into the downstream effects of CRH and Uct are required to elucidate the mechanism by which these neuropeptides could establish a stress-related pathophysiological condition in the skin.

In vitro mechanisms of interleukin-8-mediated responses of human gingival epithelial cells to Candida albicans infection

Oral epithelial cells significantly influence host inflammatory responses against Candida albicans in oropharyngeal candidiasis. We sought to elucidate the pattern of interleukin-8 (IL-8) expression by oral epithelial cells, which may function as an early innate immune system mediator during C. albicans infection. Primary human gingival epithelial cells (HGECs) were co-cultured with either viable or heat-killed C. albicans or fungal-derived substances, such as fungal secretion, fungal extracted proteins, and α-mannan. In vitro cell injury due to viable C. albicans was detectable by an adenosine triphosphate-based assay after 12 h of infection. Prior to the detection of cell injury, HGECs clearly increased production of interleukin-1 alpha (IL-1 α) and IL-8 in response to C. albicans infection, as determined by enzyme-linked immunosorbent assay and real-time reverse transcription PCR. High concentrations of a suspension of heat-killed yeast and all fungal-derived substances examined also stimulated IL-8 production by HGECs. Incubation with neutralizing anti-IL-1 α or anti-intercellular adhesion molecule-1 (ICAM-1) monoclonal antibodies (mAb) significantly inhibited C. albicans-induced IL-8 production. Use of mAbs against both IL-1 α and ICAM-1 produced a more significant combined inhibitory effect on the IL-8 production than either mAb alone. These findings indicate that HGECs synthesize increased levels of IL-1 α and IL-8 in response to viable C. albicans before cell injury is manifested. Fungal cell-wall components, α-mannan, and fungal protein extracts are all sufficient to increase IL-8 production. The molecular mechanisms governing the IL-8 response of HGECs to C. albicans infection likely involve multiple converging signal transduction pathways, including those mediated by IL-1 α and ICAM-1 activation.

The presence of endometrial cells in the peritoneal cavity enhances monocyte recruitment and induces inflammatory cytokines in mice: Implications for endometriosis

To determine the inflammatory response in the peritoneal cavity by the presence of endometrial cells and the role of the mesothelium. In vivo study using mice. University research laboratory. Female Swiss Webster mice, 8 to 10 weeks old. Homogenous mouse endometrial epithelial and stromal cells were injected intraperitoneally. Peritoneal lavage and mesothelium were collected 4 to 72 hours after the administration. We determined the number of peritoneal macrophages, and the production and gene expression of monocyte chemotactic protein-1 (MCP-1/JE), interleukin 1alpha (IL-1alpha), and interleukin 6 (IL-6). The intraperitoneal administration of endometrial cells increased the number of peritoneal macrophages, production of MCP-l, IL-1alpha, and IL-6, and expression of mesothelial MCP-1/JE, IL-1alpha, and IL-6 genes in recipient mice. These results suggest that retrograde menstruation could account for the increased presence of inflammatory mediators in the peritoneal cavity of women with endometriosis. The mesothelium could play an active role in endometriosis in addition to providing an attachment stratum for the endometrial cells.

Clinical Snippets

Mother was right: eat your spinach. And it is even better if you eat lots of kale. These are the two vegetables with the highest concentrations of lutein, a carotenoid with one additional hydroxyl group attached to each of its two aromatic rings. High serum lutein levels are associated with less retinal macular degeneration; not surprisingly, there is lots of web activity about this molecule. Granstein and his associates have shown in a mouse model that lutein depresses UVB-induced erythema response and prevents the local decrease in delayed hypersensitivity induced by UVB. In addition to further studies of lutein on UVB carcinogenesis (before the whole world is luteinized), this is the time for random double-blind studies on several of the UVB-associated acute and chronic disorders. J Invest Dermatol 122:510–517, 2004 Anderson and his team investigated damage to blood vessels induced by lasers. The photopathobiology induced by lasers requires visualization of events on the millisec scale. Using a camera to capture 2000 frames per second, the authors were able to study at short time scales the damage to blood vessels and tissues, as well as quantify individual events, such as the effect of pulse duration, fluence, and intravascular cavitation. Vessel contraction and collagen contraction were important steps in laser damage. Making smarter lasers for the desired tissue effects is next. J Invest Dermatol 122:518–525, 2004 For most patients, the usual short-term eruption of polymorphous light eruption (PMLE) after the Spring's first dose of sunlight is a minor annoyance. The mechanism of PMLE is under active study as shown by results from England. In both groups, one MED of solar simulated UV irradiation suppressed sensitization with a potent contact sensitizer less in controls than in PMLE patients. The response may be very sensitive to the UV dose. More detailed mechanistic studies in the patients may define the defect of the PMLE. J Invest Dermatol 122:291–294, 2004; J Invest Dermatol 122:295–299, 2004 Trichothiodystrophy (TTD) with photosensitivity is associated with a mutation in the XPD gene, which is essential for DNA repair. Whereas xeroderma pigmentosum patients with XPD deficiency develop skin cancers, TTD patients with XPD deficiency do not. Detailed study of DNA repair in the TTD patients showed defects with the presence of photoproducts and decreased repair proteins. Nishiwaki and colleagues concluded that the cancer-free phenotype in TTD is not related to the DNA repair defect. These rare diseases yield tantalizing clues to potential new steps or mechanisms related to skin cancer formation that should be applicable to the general population. J Invest Dermatol 122:526–532, 2004 To regenerate the barrier in aging skin, Imiquimod seems better than Viagra. Warts, skin malignancies, and vascular lesions are all improved by Imiquimod. Interleukin-1 alpha is associated with restoration of stratum corneum barrier function. In the study by Barland and coworkers, aged skin responded to barrier damage in a sluggish and not too impressive manner. Enter Imiquimod: interleukin-1 alpha production was increased and the barrier restored in the older mouse and even at a faster rate in the younger mouse. What next for Imiquimod? (The editor has no conflict of interest with either molecule and would use them if needed.) J Invest Dermatol 122:330–336, 2004

Imiquimod-induced interleukin-1 alpha stimulation improves barrier homeostasis in aged murine epidermis.

In response to acute disruption of the permeability barrier of aged mammals there is a diminished capacity for barrier recovery, analogous to other aged organs when stressed. Acute barrier disruption increases levels of epidermal cytokines, and cytokines are known regulators of keratinocyte mitogenesis, as well as lipid synthesis in extracutaneous tissues. Underlying the sluggish barrier recovery in aged skin are diminished mRNA and protein levels for the interleukin-1 cytokine family, and its receptors. To further elucidate the role of the interleukin-1 family of cytokines in the barrier repair response, cytokine production was stimulated in aged murine skin with topical imiquimod application. Imiquimod accelerated barrier recovery after acute insults to aged and young skin. These functional results correlated temporally with increased interleukin-1 alpha production in the epidermis following topical imiquimod administration to murine skin. Furthermore, intracutaneous injections of interleukin-1 alpha accelerated barrier recovery in aged mice. Finally, we showed that interleukin-1 alpha added to cultured human keratinocytes stimulates epidermal lipid synthesis. These studies provide further evidence for the role of reduced interleukin-1 alpha signaling in the decline of permeability barrier function in aged skin, and point to the potential use of cytokine augmentation in barrier dysfunction of the aged.

Heparin inhibits lipopolysaccharide (LPS) binding to leukocytes and LPS-induced cytokine production.

The glycosaminoglycan heparin is known to exhibit anti-inflammatory properties unrelated to its anticoagulant activity. However, in a generalized inflammatory response with implanted or extracorporeal devices, the beneficial effect of heparin coating and/or systemic administration is still unclear as well as the precise mechanisms of action. In the present study, we have first studied the effect of heparin on lipopolysaccharide (LPS)-induced cytokine production by human blood monocytes. Our results indicated that the production of interleukin-1alpha, tumor necrosis factor-alpha, and interleukin-8 was significantly decreased when heparin was simultaneously incubated with Escherichia coli LPS. Because the modulation of heparin on monocyte activation could be mediated by its binding via CD14, the main LPS receptor on monocytes, we then studied the binding of LPS and heparin to leukocytes from human blood and to Chinese hamster ovary cells transfected with the human CD14 gene. The data by flow cytometry showed the binding of biotinylated heparin to leukocytes. Moreover, the experiments performed on leukocytes and on CD14-positive Chinese hamster ovary cells indicated that heparin inhibited LPS binding. From our results, we conclude that: 1. heparin is an effective inhibitor of LPS-induced monocyte activation, and 2. heparin inhibits the binding of LPS to cells via a CD14-independent pathway. This study suggests a potentially important therapeutic application for heparin or heparin analogs to prevent inflammation with biomaterials.

Effect of anticonvulsant drugs on interleukins-1, -2 and -6 and monocyte chemoattractant protein-1

In order to evaluate whether treatment with valproic acid or carbamazepine can modify interleukins and monocyte chemoattractant protein-1, we studied 40 epileptic children and adolescents. We evaluated the patients before and after 1 year of therapy. At the end of follow-up, the patients showed a significant increase of the production of interleukin-1alpha, interleukin-1beta, interleukin-6, and monocyte chemoattractant protein-1; interleukin-2 production was significantly higher only in patients receiving carbamazepine. In conclusion, antiepileptic drugs can influence the immune system by modifying interleukin and chemokine concentrations; these changes seem to be independent of the serum concentrations of these drugs.

Dendritic cell activation and cytokine production induced by group B Neisseria meningitidis: interleukin-12 production depends on lipopolysaccharide expression in intact bacteria.

Interactions between dendritic cells (DCs) and microbial pathogens are fundamental to the generation of innate and adaptive immune responses. Upon stimulation with bacteria or bacterial components such as lipopolysaccharide (LPS), immature DCs undergo a maturation process that involves expression of costimulatory molecules, HLA molecules, and cytokines and chemokines, thus providing critical signals for lymphocyte development and differentiation. In this study, we investigated the response of in vitro-generated human DCs to a serogroup B strain of Neisseria meningitidis compared to an isogenic mutant lpxA strain totally deficient in LPS and purified LPS from the same strain. We show that the parent strain, lpxA mutant, and meningococcal LPS all induce DC maturation as measured by increased surface expression of costimulatory molecules and HLA class I and II molecules. Both the parent and lpxA strains induced production of tumor necrosis factor alpha (TNF-alpha), interleukin-1alpha (IL-1alpha), and IL-6 in DCs, although the parent was the more potent stimulus. In contrast, high-level IL-12 production was only seen with the parent strain. Compared to intact bacteria, purified LPS was a very poor inducer of IL-1alpha, IL-6, and TNF-alpha production and induced no detectable IL-12. Addition of exogenous LPS to the lpxA strain only partially restored cytokine production and did not restore IL-12 production. These data show that non-LPS components of N. meningitidis induce DC maturation, but that LPS in the context of the intact bacterium is required for high-level cytokine production, especially that of IL-12. These findings may be useful in assessing components of N. meningitidis as potential vaccine candidates.

Catecholamines play a role in the production of interleukin-6 and interleukin-1alpha in unburned skin after burn injury in mice.

To investigate the effects of catecholamines on the production of interleukin (IL)-6 and IL-1alpha in unburned skin after a burn injury. Randomized, controlled study. Animal laboratory. Anesthetized female C57BL/6 mice. A full-thickness burn injury on 20% of total body surface area was produced on the clipped dorsum, which was followed by resuscitation with lactated Ringer's solution (0.1 mL/g). Phentolamine mesylate (10 mg/kg) or propranolol hydrochloride (10 mg/kg) was administered intraperitoneally before the burn injury. Epinephrine and norepinephrine increased the production of IL-6 but not of IL-1alpha in normal abdominal skin, and these increases were reversed by a beta-blocker (propranolol hydrochloride) but not an alpha-blocker (phentolamine mesylate). A 20% full-thickness burn injury of the skin increased the plasma concentration of epinephrine 30 mins after the injury in female C57BL/6 mice, but not norepinephrine or dopamine. The burn also increased IL-6 production in unburned abdominal skin. The administration of a beta-blocker before a 20% burn injury suppressed the increased IL-6 production in unburned abdominal skin as determined by both protein level and mRNA expression. Pretreatment with the alpha-blocker was less effective. We propose that the neuroendocrine system activated by a 20% burn injury participates in the increased IL-6 production in the unburned skin.

Glucocorticoids Augment the Chemically Induced Production and Gene Expression of Interleukin-1α through NF-κB and AP-1 Activation in Murine Epidermal Cells

To clarify the mechanism of the glucocorticoid-induced augmentation of skin response, we attempted to demonstrate the modulatory effect of glucocorticoids on the regulation of cytokines produced by keratinocytes stimulated with various chemicals in vitro. Haptens, irritants, and a superantigen (staphylococcal enterotoxin B) induced a significant release of interleukin-1alpha and tumor necrosis factor alpha, but not interleukin-10, from a murine keratinocyte cell line, Pam 212 cells. Glucocorticoids (10(-6)-10(-12) M) significantly augmented the production of interleukin-1alpha by Pam 212 cells at both the protein and mRNA levels when stimulated by either haptens or irritants, but not by staphylococcal enterotoxin B, whereas glucocorticoids alone had no effect. In contrast, glucocorticoids had no effect on the production of tumor necrosis factor alpha and interleukin-10 by chemically stimulated Pam 212 cells. Electrophoretic mobility shift assays revealed that chemical stimulation induced NF-kappaB activation in Pam 212 cells; however, augmented NF-kappaB activation by 10(-6)-10(-8) M of glucocorticoids was observed in Pam 212 cells stimulated by both haptens and irritants, but not by staphylococcal enterotoxin B. Furthermore, pyrrolidine dithiocarbamate inhibited the hapten-induced interleukin-1alpha production and NF-kappaB expression by Pam 212 cells. Pyrrolidine dithiocarbamate did not completely abrogate the hapten-induced interleukin-1alpha production augmented by glucocorticoids, however. To determine the effect on transcription factors other than NF-kappaB, AP-1 activity was examined by electrophoretic mobility shift assays. Hapten was founded to induce AP-1 activation in Pam 212 cells. In addition, AP-1 activation was augmented in the hapten-stimulated Pam 212 cells in the presence of 10(-8)-10(-10) M of glucocorticoids. The augmented inflammatory reaction by glucocorticoids may therefore reflect the augmentation of interleukin-1alpha production by keratinocytes mediated through the NF-kappaB and AP-1 pathway.

Inflammatory cytokine production by immunological and foreign body multinucleated giant cells.

Multinucleated giant cells (MGC) are a common feature of granulomas. The mechanism of their formation has been studied extensively, but their function has not been completely characterized. A new method for the in vivo production of MGC was developed involving subcutaneous injection of microscopic nitrocellulose particles with adsorbed mycobacterial antigens into the footpads of sensitized BALB/c mice (immune [I]-MGC), or by nitrocellulose administration to non-sensitized mice (foreign body [FB]-MGC). The development of granulomas with a highly enriched MGC population was observed 2 weeks after the nitrocellulose injection. MGC were larger with a greater number of nuclei in I-MGC than in FB-MGC. From days 7-28 after nitrocellulose administration, the production of interleukin-1alpha (IL-1alpha) and tumour necrosis factor-alpha (TNF-alpha) was demonstrated in both MGC types by in situ reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. After 2 months, the MGC had ceased production of IL-1alpha and TNF-alpha, but the expression of transforming growth factor-beta (TGF-beta) was very high, occurring together with extensive fibrosis. These results suggest that MGC are an active source of inflammatory cytokines, which can contribute to the initiation, maintenance and down-regulation of granulomatous inflammation induced by immunological and inert substances.

Effect of grepafloxacin on cytokine production in vitro

The effect of a new quinolone antibacterial agent, grepafloxacin, on the production of cytokines was investigated using lipopolysaccharide-stimulated human peripheral blood cells. Grepafloxacin 1-30 mg/L inhibited the production of interleukin 1alpha (IL-1alpha) and IL-1beta, and the expression of IL-1alpha, IL-1beta, tumour necrosis factor alpha (TNFalpha), IL-6 and IL-8 mRNA. These results suggest that the inhibitory effect of grepafloxacin is exerted, in part, at the gene transcription level.