Changes In Cytokine Concentrations Research Articles

Changes in cytokine concentrations following successful ablation of atrial fibrillation.

Atrial fibrillation is associated with the activation of inflammatory processes [e.g. higher concentrations of pro-inflammatory cytokines interleukin-6 (IL-6), C-reactive protein (CRP)], as well as a pro-thrombotic state [e.g. increased concentration of serum pro-thrombotic markers P-selectin and CD40 ligand (CD40L)]. The aim of the present study was to establish, whether successful epicardial ablation of AF leads to decreased concentrations of traditional inflammatory and thrombotic markers. Twenty-five patients with symptomatic paroxysmal or persistent AF were prospectively studied. All underwent epicardial isolation of pulmonary veins. The success of the ablation was assessed clinically and with three Holter recordings. Blood samples were drawn before, three and six months after surgery. Serum concentrations of IL-6, interleukin-10 (IL-10), CRP, CD40L and P-selectin were measured using ELISA. AF was successfully ablated in 15 patients (SR group). In the other 10 patients (AF group), AF re-occurred during follow-up. Neither group differed with respect to age, gender, left ventricular ejection fraction, or preoperative concentrations of measured molecules. The concentrations of IL-6, CRP and CD40L decreased in successfully ablated patients; however, there was no change in the concentrations of these molecules in the AF group. The concentrations of IL-10 and P-selectin were unchanged in both groups during follow-up. Successful ablation of AF, with sinus rhythm restoration and maintenance, is associated with decreased serum levels of markers of inflammation.

RANKL and OPG activity is regulated by injury size in networks of osteocyte-like cells

Bone remodelling is an intricate process encompassing numerous paracrine and autocrine biochemical pathways and mechanical mechanisms. It is responsible for maintaining bone homeostasis, structural integrity and function. The RANKL-RANK-OPG cytokine system is one of the principal mediators in the maintenance of bone cell function and activation of bone remodelling by the Basic Multicellular Unit (BMU) which carries out remodelling. Theories surrounding the initiation of bone remodelling include mechanical loading, fluid flow and microdamage as potential stimuli. This study focused on microdamage. In an in vitro simulated bone environment, gel embedded MLO-Y4 cell networks were subjected to damage in the form of planar, crack-like defects of constant area and varying thickness. The biochemical response was determined by ELISA and luciferase assay. The results showed that RANKL release increased and OPG decreased in a manner which depended on injury size (i.e. thickness) and time following application of injury. The effect of microdamage on cell viability and apoptosis was also evaluated. This work demonstrates that injury alone, in the absence of imposed strain or fluid flow, is sufficient to initiate changes in cytokine concentrations of the type which are known to stimulate bone remodeling.

Depression, mood, stress, and Th1/Th2 immune balance in primary breast cancer patients undergoing classical massage therapy

Cancer patients frequently suffer from psychological comorbidities such as depression and elevated stress. Previous studies could demonstrate that cancer patients benefit from massage therapy on the physical and psychological level. This pilot study investigates the effects of massage on depression, mood, perceived stress, and the Th1/Th2 ratio in breast cancer patients. Thirty-four breast cancer patients were randomly assigned to a massage group (n=17) and a control group (n=17). Patients of the massage group received two 30-min classical massages per week for 5 weeks. At baseline, at the end of the intervention period, and 6 weeks after the end of intervention, patients of both groups completed the Perceived Stress Questionnaire (PSQ), the Patient Health Questionnaire (PHQ), and the Berlin Mood Questionnaire (BFS) and blood was withdrawn for determining cytokine concentrations and the Th1/Th2 ratio. Twenty-nine patients were included in the statistical analysis. Depression (PHQ) and anxious depression (BSF) were significantly reduced immediately after massage compared to the control group. Stress (PSQ) and elevated mood (BSF) did not show significant alterations after massage therapy. Changes of cytokine concentrations and Th1/Th2 ratio were insignificant as well, although there was a slight shift towards Th1 in the massage group over time. Massage therapy is an efficient treatment for reducing depression in breast cancer patients. Insignificant results concerning immunological parameters, stress, and mood indicate that further research is needed to determine psychological and immunological changes under massage therapy.

A single dose of vitamin A improves haemoglobin concentration, retinol status and phagocytic function of neutrophils in preschool children

Since there is a reported interrelationship between vitamin A and Fe metabolism, and with immunological response, the objective was to evaluate the effect of a single dose of vitamin A administered to preschool children, on Fe and vitamin A nutritional status, anaemia and phagocytic function of neutrophils, 30 d after supplementation. A total of eighty children (sixty-eight supplemented and twelve controls) were supplemented orally with 200,000 IU (60 mg) vitamin A, and evaluated for nutritional, haematological and immunological responses at the beginning of the study and 30 d after supplementation. Parameters studied included Hb, serum ferritin, retinol and Fe concentrations, transferrin saturation, IL-4, interferon-gamma and phagocityc capacity of neutrophils using non-fluorescent latex microbeads. After supplementation there was a significant increase in Hb concentration (P = 0.03), mean corpuscular Hb concentration (P = 0.001) and serum retinol (P = 0.0078). Prevalences of anaemia and vitamin A deficiency decreased significantly from 17.6 % to 13.2 % and from 25 % to 13.2 %, respectively. Regarding phagocytic function, there was a significant increase in the number of microbeads engulfed by neutrophils (P < 0.05) and no significant changes in cytokine concentrations at 1 month after treatment. A single dose of 200,000 IU (60 mg) vitamin A administered orally to a group of preschool children with a high prevalence of vitamin A deficiency enhanced serum retinol and Hb concentrations, decreased the prevalence of anaemia and vitamin A deficiency and improved the constitutive phagocytic capacity of neutrophils. Vitamin A supplementation could help to decrease vitamin A deficiency, anaemia prevalence and to improve the innate immunity response in preschool children. The effects were obtained without Fe supplementation.

Exogenous Soluble VEGF Receptor-1 (sFlt-1) Regulates Th1/Th2 Cytokine Production from Normal Placental Explants via Intracellular Calcium

Objective: The increase of soluble VEGF-Receptor 1 (sFlt-1) is thought to contribute to the pathogenesis of preeclampsia. Soluble VEGF-Receptor 1 binds to circulating free VEGF and PLGF and this cascade is associated with endothelial dysfunction, a prominent feature of preeclampsia. Preeclampsia is also associated with excessive maternal response to pro-inflammatory stimuli manifesting as an imbalance of Th1/Th2 cytokine production at the maternal-fetal interface. Whether increased sFlt-1 expression has any effect on placental production of Th1/Th2 cytokines IL-10 and TNF-α is yet to be investigated. The aim of this study is to examine if exogenous sFlt-1 can regulate Th1/Th2 cytokines IL-10 and TNF-α production from normal placental explants via intracellular calcium release. Methods: Placental explants were taken from the decidual surface of normal non-laboured term placentas (n = 11).Villous explants were cultured with increasing concentrations of sFlt-1. The dose effect of sFlt-1 on placental Th1 and Th2 cytokine production (TNF-α and IL-10) were examined. Free PLGF, VEGF and sFlt-1 concentrations in the conditioned medium were also measured. Intracellular calcium blocker, 1,2-bis-(o-aminophenoxy)-ethane-N,N,N′,N′-tetraacetic acid, tetra(acetoxymethyl)-ester (BAPTA/AM) was applied to investigate whether the changes in cytokine concentration were mediated by intracellular free calcium. Results: Placental IL-10 and TNF-α production were significantly increased after sFlt-1 incubation. The increase in IL-10 can be inhibited by BAPTA/AM. Soluble Flt-1 and free PLGF concentration in the conditioned medium was not changed. Free VEGF concentration in the conditioned medium was not detectable. Conclusion: Exogenous sFlt-1 can increase TNF-α and IL-10 production from normal placental explants. The change in Th1/Th2 cytokine level may be mediated by intracellular free calcium.

Ras inhibition increases the frequency and function of regulatory T cells and attenuates type-1 diabetes in non-obese diabetic mice

Regulatory T cells (Treg) reportedly suppress diabetes in non-obese diabetic (NOD) mice, and the frequency and functional suppressive properties of Treg were found to be upregulated by inhibition of Ras. We thus postulated that treatment with the Ras inhibitor 5-fluoro-farnesylthiosalicylic acid (F-FTS), a derivative of S-farnesylthiosalicylic acid (FTS), would attenuate diabetes development in NOD mice. To test this hypothesis we assayed Foxp3, total Ras, and GTP-Ras in NOD splenocytes following their exposure to FTS and F-FTS in vitro. In splenocytes exposed to FTS, and even more so to F-FTS, Foxp3 expression was increased and GTP-Ras expression reduced. We also injected NOD mice intraperitoneally with F-FTS and assessed both their Treg pools and the occurrence of diabetes. The treated mice showed a significant increase in the frequency of spleen-cell-derived Foxp3+ Treg, and their Treg were more effective than Treg from untreated NOD controls in suppressing the proliferation of effector T cells. Moreover, the F-FTS treatment also attenuated the development of diabetes in the NOD mice. The mice were then killed and their insulin and cytokine levels assayed. The treated mice showed an increase in circulating insulin but no change in cytokine concentrations. One of the mechanisms underlying our novel finding that treatment with a Ras inhibitor ameliorates the development of experimental type-1 diabetes could thus conceivably be an augmentation in the frequency and functional suppressive properties of Treg. Ras inhibition might therefore be worth developing as a new treatment modality in patients with type 1 diabetes.

Relationships between adipose tissue and cytokine responses to a randomized controlled exercise training intervention

Adipose-derived cytokines play a prominent role in mediating the metabolic consequences of obesity and excess body fat. Given this, we hypothesized that alterations in adipose tissue stores incurred with exercise training would be reflected in changes in systemic cytokine concentrations. The Studies of Targeted Risk Reduction Intervention through Defined Exercise, where pronounced changes in adipose tissue stores were observed in the absence of significant changes in dietary intake, provided an ideal setting in which to test this hypothesis. Participants were randomized to 6 months of inactivity or one of 3 types of aerobic exercise training regimens: low-amount-moderate-intensity, low-amount-vigorous-intensity, and high-amount-vigorous-intensity. Plasma samples were collected at baseline and 2 weeks after cessation of 6 months of exercise training or inactivity. In 189 participants, concentrations of 17 cytokines were measured using Bio-Plex Cytokine Assays (Bio-Rad, Hercules, CA); 10 additional cytokines were measured in 60 of these subjects. Of all cytokines tested, the only concentration changes that approached statistical significance were those for granulocyte monocyte–colony stimulating factor and vascular endothelial growth factor, which appeared to increase with training in the low-amount-high-intensity group only ( P < .05 for both cytokines). No response to exercise training was noted for any additional cytokine in any of the groups. No relationships were observed between changes in cytokine concentrations and changes in fat mass or other measures of body habitus. In contradiction to our hypothesis, despite significant alterations in body composition, exercise training produced limited cytokine responses.

Escherichia coliによる乳牛の甚急性乳房炎における血清中および乳清中サイトカインの動態と臨床症状

<I>Escherichia coli</I>による乳牛の甚急性乳房炎における血清中および乳清中サイトカインの動態と臨床症状

Evaluation of Ten Cytokines in Response to Treatment of Active UC

Purpose: There exists no reliable blood biomarker of the activity of UC. Although CRP is widely used in clinical practice, it has limitations. Cytokines that reflect Th1 and Th2 activity are other potential candidates. This pilot study examines the relationship between clinical criteria of activity and the cytokine levels in patients with active UC. Methods: Samples from 21 patients with moderately active UC (Mayo score 7–11) were recruited after informed consent. Blood samples were taken before and after treatment from each patient. Samples were analysed for concentrations of IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IFN-γ and TNF-α using a manufacturer defined protocol. Logistic regression was used to model post-treatment Mayo scores as a function of baseline cytokine concentration and the change in cytokine concentration after treatment. Cytokine concentration was correlated with treatment outcome, symptoms (stool frequency and rectal bleeding), endoscopic appearance, extent of UC and between biomarkers. Results: The model identified a relationship between baseline [IL-5], [IL-8] and [IL-10] and response to treatment, (βIL-5 = -1.1, P= 0.142, βIL-8 = -0.07, P= 0.070, βIL-10 = -0.18, P= 0.034), but its predictive ability was weak. Higher baseline [IL-5] and [IL-8] and lower [IL-10] predicted lower post-treatment Mayo scores. The relationship was strongly influenced by data outliers. Modelling the change in cytokine concentration identified only Δ[IL-2] as potentially associated with treatment outcome (P= 0.0003). Positive Δ[IL-2] correlated with higher post treatment Mayo scores. The relationship was not robust and had weak predictive ability. Concentrations of IL-2, IL-4, IL-12, IFN-γ and TNF-α all correlated with each other (all P < 0.0001), but neither individually nor in combination with treatment outcome, clinical or endoscopic criteria of response. Conclusion: Neither baseline nor changes in cytokine concentrations, either singly or in combination, were sufficiently robust to predict treatment response in this pilot study. Nevertheless, the combination of baseline [IL-5], [IL-8] and [IL-10], or change in [IL-2] are worth exploring in larger studies. Multiplex biomarker analysis has the potential for evaluating host response to the disease activity. Clear correlations between IL-2, IL-4, IL12, IFN-γ and TNF-α in patients with active UC support the concept of a balance between Th1/Th2 responses in acute colitis.

Cytokines at different stratum corneum levels in normal and sodium lauryl sulphate‐irritated skin

Cytokines play an important role in inflammatory and repair processes occurring in the skin. The objectives of this study were to determine the amounts of cytokines and protein isolated by tape stripping in the different layers of the stratum corneum (SC), and to compare normal skin with skin exposed in vivo to the irritant sodium lauryl sulphate (SLS). In eight volunteers, we determined the amount of total and soluble protein and also interleukin-1alpha (IL-1alpha) in pooled tape strips obtained from the upper, intermediate and lower parts of the SC. Three different types of tape were compared (Diamond , D-squame or Sentega tape). In a separate study, 20 volunteers were repeatedly exposed to 0.1% SLS over a 3-week period. The amounts of IL-1alpha, IL-1RA and IL-8 in strips obtained from the three different SC levels of SLS-exposed skin were compared with an unexposed site. For normal skin, the amounts of soluble protein and IL-1alpha were similar for the three tapes. Diamond tape showed the highest yield of total protein. The total protein yield per strip decreased to lower SC levels, whereas soluble protein and IL-1alpha normalized by soluble protein did not change across the SC. After SLS induced skin irritation, IL-1alpha decreased and IL-1RA and IL-8 increased at increasing depth into the SC. Tape stripping is a suitable method to determine SC cytokine concentrations in human skin. With this technique, it is possible to study changes in cytokine concentrations at different SC layers after skin irritation.

Intrathecal betamethasone pain relief in cancer patients with vertebral metastasis: a pilot study

We have reported previously the usefulness of intrathecal betamethasone for pain relief in cancer patients who suffer from intractable pain caused by vertebral metastasis. The mechanism by which betamethasone relieves pain may be related to alterations in cerebrospinal fluid (CSF) concentrations of pro-inflammatory cytokines and prostanoids. Thirteen cancer patients with intractable pain caused by vertebral metastasis received 2-3 mg betamethasone in the lumbar subarachnoid space. CSF concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-8 and prostaglandin E(2) (PGE(2)) were measured with an enzyme-linked immunosorbent assay (ELISA) and a chemiluminescence enzyme immunoassay. Pain was measured using a numerical pain score (range, 0-10; 0, no pain; 10, worst pain imaginable). Intrathecal betamethasone was associated with a significant decrease in the pain score in six patients. In these cases, the pain score decreased from 6.7 +/- 0.5 (mean +/- standard error of the mean) to 3.3 +/- 0.3 (P < 0.05), and the CSF concentrations of IL-8 and PGE(2) decreased significantly compared with pre-treatment levels (IL-8, 183.3 +/- 21.2 to 116.5 +/- 10.6 pg/ml; PGE(2), 43.8 +/- 10.3 to 14.7 +/- 3.0 pg/ml). There were no significant changes in the CSF concentrations of cytokines and PGE(2) in the remaining seven patients. Pain relief with intrathecal betamethasone is related to decreases in the CSF concentration of IL-8 and PGE(2).

Changes in cytokine concentration during enrichment of early enteral nutrition with lactic acid bacterium (Synbiotic 2000) after major abdominal surgery

Changes in cytokine concentration during enrichment of early enteral nutrition with lactic acid bacterium (Synbiotic 2000) after major abdominal surgery

Effect of oral glucocorticoid treatment on serum inflammatory markers in acute asthma

BACKGROUNDAcute asthma is associated with elevated serum concentrations of products of activated T cells and eosinophils.AIMSTo compare the changes in concentrations of these products with disease severity and changes in...

Cytokine abundance in placental tissues: Evidence of inflammatory activation in gestational membranes with term and preterm parturition

Objectives: This study of the changes in cytokine concentrations in gestational tissues from women with term and preterm labor was undertaken to assess the extent of inflammatory activation associated with spontaneous labor and delivery. Study Design: Extracts of amniotic, chorionic-decidual, and placental tissues from women delivered at term before labor (n = 15), at term after labor (n = 15), and preterm (n = 31) were assayed for interleukin 1β, interleukin 6, and interleukin 8. Results: In amniotic tissues of women delivered by spontaneous labor at term the median interleukin-6, interleukin-8, and interleukin-1β concentrations were 3.8 to 5.4 times those of tissues from women delivered at term without labor (P < .05, Mann-Whitney U test). Interleukin-6 and interleukin-8 concentrations were also significantly increased (3.3-4 times) in chorionic-decidual tissues. Marked increases (approximately 3-6 times) in the concentrations of all 3 cytokines were observed in both amniotic and chorionic-decidual tissues from women with preterm deliveries with respect to those from women with term deliveries after labor. Cytokine concentrations were significantly correlated within amniotic tissues from both women with term delivery after labor and women with preterm delivery and also in preterm chorionic-decidual tissues but not preterm placental tissues. Concentrations of cytokines in the tissues of women delivered preterm were not significantly affected by mode of delivery, treatment with antibiotics, or twin birth. In preterm tissues with evidence of intrauterine infection only amniotic interleukin-1β concentrations were significantly elevated (P < .05). Little or no labor-related change in cytokine concentrations was seen within placental tissues. Conclusions: Increased cytokine abundance in gestational membranes associated with labor supports the view that an inflammatory process is involved in both term and preterm labor. This process does not, however, appear to be evident in the villous placenta. (Am J Obstet Gynecol 1999;181:1530-6.)

Systemic and Cell-Mediated Immune Response after Laparoscopic and Open Cholecystectomy in Patients with Chronic Liver Disease

Background: As impaired immune function observed in cirrhotic patients is known to increase the risk of postoperative complications, the immunological response to surgery was investigated. Methods: Twenty-eight patients with postnecrotic liver cirrhosis or chonic hepatitis C and symptomatic gallstone disease were randomly allocated to laparoscopic (LC) or open cholecystectomy (OC). Changes in concentrations of cytokines (TNF-α, IL-1β, IL-6, IL-8 and IL-10) were followed and the effect of surgical trauma on the distribution of lymphocyte subpopulations (CD3, CD4, CD8, CD16 and CD19) and NK cell cytotoxicity were measured. Results: After OC a decrease in circulating CD3 (p < 0.05) and CD4 (p < 0.05) and an increase in CD19 (p < 0.05) cells were detected in contrast to LC after which only CD16 cells decreased (p = 0.05). The number of CD3 cells was higher after LC than after OC (p < 0.01), whereas the number of CD19 cells was higher after OC than after LC (p < 0.01). NK cell cytotoxicity was reduced after LC (p < 0.05). In cirrhotic patients circulating cytokines were unaffected by OC, whereas TNF-α (p < 0.05) and IL-1β (p < 0.05) were reduced after LC. In chronic hepatitis IL-1β decreased after OC (p = 0.05) and IL-10 was significantly higher after LC than following OC (p < 0.05). Conclusion: The immune response is less pronounced after a laparoscopic procedure compared to a conventional approach in patients with chronic liver disease.

Immunologic Adaptations During Pregnancy

Many complementary changes occur in a pregnant woman's immune system to protect the fetus from attack while maintaining maternal defenses against disease. Enhancements occur in immune elements that fight bacterial infections. Conversely, suppression of T-cell activity causes increased susceptibility to viral infections, such as hepatitis, rubella, herpes, and human papilloma virus, and leads to an irreversible reduction in helper T cells in women infected with the human immunodeficiency virus. Local secretion of corticosteroids and changes in cytokine concentration in the reproductive tract protect the fetus from rejection. Understanding these changes assists the perinatal nurse in assessing and counseling women of childbearing age.

Sepsis and fat metabolism

Sepsis is a common surgical problem which can induce profound changes in the plasma concentrations of cytokines and hormones, leading to a catabolic state. Hypertriglyceridaemia and increased fat oxidation are the main features of altered fat metabolism encountered in this state. The endogenous catabolism of sepsis can be reduced by administering exogenous lipid emulsions as a source of metabolic fuel, although the changes in lipid metabolism associated with sepsis may affect the handling of these exogenous lipids. An exciting area for future research is an examination of the ability of lipid emulsions to reduce the morbidity and mortality associated with sepsis by altering immune responses, in addition to limiting catabolism.

Effect of exercise on endotoxin shock with special reference to changes in concentration of cytokines.

The effects of exercise on susceptibility to endotoxin shock and the serum levels of interleukin-1 (IL-1) and interleukin-6 (IL-6) were studied in mice primed with Propionibacterium acnes (P. acnes, 1.0 mg). Endotoxin shock was induced by injection of lipopolysaccharide (LPS, 0.2 mg) 7d after the priming injection of P. acnes. The exercise-loaded mice performed voluntary exercise for 120 min on a running-wheel and LPS was injected into the tail vein immediately after the end of exercise. Two of the nine animals in the exercised group survived, whereas all the mice in the control group died. The mean survival time after LPS injection in the exercised group (10.75 +/- 4.51 h) was significantly longer than that in the control group (3.3 +/- 1.34h). The serum concentrations of IL-1 (2,883 +/- 1,542 U/ml) and IL-6 (966 +/- 619 ng/ml) in the exercised group, sampled 2h after LPS challenge, were significantly lower than those in the control group (6,571 +/- 2,766 U/ml and 2,428 +/- 1,228 ng/ml, respectively). It is suggested that the exercise-induced inhibition of endotoxin shock may be caused, at least partly, by the decreased production of IL-1 and IL-6.

Production of systemic and hypothalamic cytokines during the early phase of endotoxin fever.

Changes in concentrations of cytokines in plasma and in hypothalamic push-pull perfusates of guinea pigs were measured within the 1st hour after intramuscular injections of bacterial lipopolysaccharide (LPS; Escherichia coli, 20 micrograms/kg) or solvent (0.9% saline). In control animals injected with solvent, interleukin (IL)-1 and tumor necrosis factor alpha (TNF-alpha) were not detectable in plasma. Only IL-6 was present in picogram quantities. Within 45 min after injection of LPS, the concentrations of IL-1, TNF-alpha, and IL-6 increased in the plasma: by several orders of magnitude for TNF-alpha and about tenfold for IL-G. Picogram amounts of biologically active IL-1 were detected in plasma after injection of LPS. No steady state levels of systemic cytokines were reached during the experimental period. In hypothalamic perfusates of animals injected with the solvent, no IL-1 was detectable. TNF-alpha could be detected at higher concentrations than IL-6. IL-6 was detectable at tenfold lower concentrations than in the plasma. In animals injected with LPS, the hypothalamic concentration of IL-6 started to increase during the period 15-30 min and the concentrations of TNF-alpha during the period 30-45 min after LPS injection. The concentrations of IL-6 increased by 300-400% and did not exceed picogram values. No progressive increase of hypothalamic levels of these cytokines was observed during the time course of the experiment. The method used did not detect any changes in the amount of biologically active IL-1 in hypothalamic perfusates of LPS-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of interleukin 1, interleukin 6 and tumour necrosis factor alpha in mouse uterus during the peri-implantation period of pregnancy.

Interleukin 1 (IL-1), IL-6 and tumour necrosis factor alpha (TNF-alpha) are expressed in the mouse uterus on days 1-3 of pregnancy. Cytokine production is temporally associated with the post-mating intrauterine acute inflammatory response. In this study, IL-1, IL-6 and TNF-alpha were detected in the uterus of pregnant mice from day 3 to day 9, using northern blotting, bioassays and immunocytochemistry. IL-1 bioactivity increased from a low concentration on day 3 to a peak between days 4 and 5 and decreased to low concentrations on days 7 and 8. Blastocyst implantation occurs late on day 4. IL-6 bioactivity was high from day 3 to day 9 and activity was maximal on days 5 and 6. TNF-alpha bioactivity increased from its lowest concentration on day 3 to a peak on day 8. Although changes in bioactivity concentrations occurred at different times from changes in mRNA concentrations, the changes were approximately parallel. Translation of mRNA into an immunologically detectable product was confirmed using immunocytochemistry with polyclonal anti-cytokine antibodies. We conclude that the cytokines IL-1, IL-6 and TNF-alpha are produced in the uterus during the peri-implantation period of pregnancy in mice. Changes in cytokine concentrations suggested the existence of some form of regulated expression.