Activity Of Peritoneal Exudate Cells Research Articles

Inactivated Actinobacillus suis in Synergy with Interferon-α Protects Mice against Herpes Simplex Virus-2 Infection

AbstractA single intraperitoneal administration of heat-killed and lyophilized cells of Actinobacillus suis ATCC 15557 (AS preparation) into 5-week-old female BALB/c mice led to potent, but not statistically significant, nonspecific resistance to intravenous challenge with a lethal dose of herpes simplex virus, type 2 (HSV-2). A combination treatment with the intraperitoneal AS preparation and intravenous interferon (IFN)-α markedly elevated the survival rates of the mice. The production of endogenous IFN-γ was also enhanced by the combination treatment but the production of other endogenous cytokines such as tumor necrosis factor α and interleukin-12 was minimal. The focus of in vitro formation of HSV-2 was markedly inhibited by the peritoneal exudate cells induced by AS preparation in combination with IFN-α. The antiviral activity of peritoneal exudate cells induced by the combined agents was transferrable to syngeneic recipient mice. These results suggest the possibility that the AS preparation in combination with IFN-α may play an important role in controlling intracellular HSV-2 infection through the activation of immunocompetent cells and the production of endogenous IFN-γ in BALB/c mice.

Interleukin-12 (IL-12) and IL-18 synergistically induce the fungicidal activity of murine peritoneal exudate cells against Cryptococcus neoformans through production of gamma interferon by natural killer cells.

We examined the ability of interleukin-12 (IL-12) and IL-18 to induce the production of gamma interferon (IFN-gamma) and nitric oxide (NO) by murine peritoneal exudate cells (PEC) and to stimulate the growth-inhibitory activity of these cells against Cryptococcus neoformans. PEC produced IFN-gamma and NO when stimulated with a combination of IL-12 and IL-18 but little or no IFN-gamma or NO when either cytokine was used alone. PEC anticryptococcal activity was mediated by IFN-gamma and NO production, since it was completely inhibited by a neutralizing anti-IFN-gamma monoclonal antibody (MAb) and N(G)-monomethyl-L-arginine, a competitive inhibitor of NO synthesis, respectively. To identify the IFN-gamma-producing cells among PEC stimulated with IL-12 and IL-18, we depleted NK cells, gammadelta T cells, or CD4+ T cells by treating PEC with specific Abs and complement. NK cell depletion strongly suppressed IFN-gamma production and almost completely inhibited NO production and anticryptococcal activity, while depletion of other cells had no such influence. Alternatively, purified NK cells by two cycles of glass adherence and magnetic separation with anti-CD3, -CD4, -CD8, and -B220 MAbs produced a greater amount of IFN-gamma by stimulation with IL-12 and IL-18 than unseparated non-glass-adherent PEC. Our results demonstrated that IL-12 and IL-18 synergistically induced NO-dependent anticryptococcal activity of PEC by stimulating NK cells to produce IFN-gamma.

Effect of dietary flaxseed on fatty acid composition, superoxide, nitric oxide generation and antilisterial activity of peritoneal macrophages from female Sprague-Dawley rats.

The impact of ground flaxseed (FS) or flaxseed meal (FSM) diets on the fatty acid composition and functions of rat peritoneal exudate cells (PEC) was determined. Female weanling Sprague-Dawley rats (10/group) were fed isocaloric AIN-76 diets supplemented with 0.0, 10.0% (w/w) FS or 6.2% (w/w) FSM. At the end of 56-days, rat serum and thioglycollate-elicited PEC were analyzed for total lipid fatty acids. Production of nitric oxide (NO) and superoxide (O2-), Listeria monocytogenes (LM) phagocytic index and antilisterial activity of resident PEC were also assessed. A significant increase in alpha-linolenic (C18:3), eicosapentanoic (C20:5) and docosahexanoic (C22:6) acids, as well as a significant reduction in arachidonic acid (C20:4) was observed in the serum of rats fed 10% FS. Dietary FS caused a significant reduction in palmitic acid (C16:0) and an increase in stearic acid (C18:0) of PEC. Defatted FSM produced a significant increase in long chain fatty acids, which included eicosadienoic acid (C20:2) in PEC and C22:6 in serum. PEC from rats fed 10.0% FS produced significantly less (about 50%) O2- in response to phorbol myristate acetate (PMA), than did PEC from control animals; dietary treatment had no effect on O2- in response to LM. FSM had no impact on the O2- production by PEC in response to PMA or LM. Antilisterial activity of PEC was determined by comparing bacterial uptake after 1 hr with recovery 24 hrs later. Despite comparably equivalent bacterial uptake, few viable intracellular LM were recovered at T = 24 for all test samples, indicating that, regardless of the dietary treatment, PEC were able to handle the in vitro LM infection. This bacterial clearance was accompanied by equivalent NO generation by PEC from each dietary group in response to LM. Summarily, dietary FS produced significant changes in fatty acid composition of serum and PEC, inhibited O2- generation by PEC, and was ineffectual to both NO production by and antilisterial activity of PEC.

In vivo macrophage-stimulation activity of the enzyme-degraded water-soluble polysaccharide fraction from a marine alga (Gracilaria verrucosa).

The water-soluble polysaccharide fraction from Gracilaria verrucosa (GWS) has been reported to increase the phagocytic activity of mice [Yoshizawa et al., Nippon Shokuhin Kogyo Gakkaishi, 41, 557-560 (1994)]. In this study, the macrophage-stimulation activity of enzyme-degraded GWS (GWS-E) was investigated by intraperitoneally and orally administering GWS-E to mice. The intraperitoneal administration of GWS-E increased the number of peritoneal exudate cells (PEC), and increased the phagocytic activity and oxygen radical-secreting activity (spontaneous chemiluminescence) of PEC. This administration could also stimulate splenic macrophages (SPM), increasing radical-secreting activity. When GWS-E was administered orally, the radical-secreting activity of PEC and SPM increased. In this case of oral administration, the activity of SPM increased in a dose-dependent manner, while that of PEC had an optimum dose. These results indicate that GWS-E had macrophage-stimulation activity in vivo and would be suitable as a source for a physiologically functional food with protective and immunopotentiating activity.

Enhancement of host resistance to bacterial infections in normal and immunosuppressed mice with Actinobacillus suis.

A single intraperitoneal (ip) inoculation of heat-killed Actinobacillus suis ATCC 15,557 (AS 15,557) into normal and immunosuppressed (dexamethasone-treated) mice led to remarkable nonspecific resistance to ip challenge with lethal doses of opportunistic pathogens such as Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus and Candida albicans. The duration of this enhanced protective action and the minimal effective dose, in normal mice, induced by AS 15,557 were superior to those induced by other bacterial immunostimulants such as heat-killed Lavtobacillus casei YIT 9018 (LC 9018) and penicillin-treated Streptococcus pyogenes, Su (OK-432). In immunosuppressed mice; the reduced in vivo killing activity of peritoneal exudate cells (PECs) against P. aeruginosa infection was markedly augmented by ip injection of AS 15,557. The degree of PEC augmentation induced by AS 15,557 was higher than that induced by LC 9018 or by OK-432. The toxicity and histopathological changes associated with AS 15557 were very low, as compared with those by produced by LC 9018 and OK-432. The results suggest that AS 15,557, which showed a strong resistance-enhancing capacity against opportunistic bacterial infections, may be a useful bacterial immunostimulant.

Interleukin-5 induces tumor suppression by peritoneal exudate cells in mice.

The antitumor activity of peritoneal exudate cells (PEC) induced by murine interleukin-5 (mIL-5) was examined using Meth-A sarcoma cells transplanted into the peritoneal cavity of mice. Although in vitro treatment of Meth-A sarcoma cells with mIL-5 did not result in inhibition of their growth, treatment of mice intraperitoneally with mIL-5 (1 microgram/day) from day -5 to +5 (tumor cells were inoculated on day 0) led to a significant increase in survival or even rejection of tumor cells. This antitumor effect depended on the dose of mIL-5. Interestingly, there was identical therapeutic activity when the protocol of days -10 to -1 was used as opposed to -5 to +5. In addition, post-treatment with mIL-5 from day +1 to +10 was ineffective. This suggests that the therapeutic activity of IL-5 is largely prophylactic. Under the former condition, the number of PEC was found to increase over 50-fold when compared to levels in control mice. Moreover, the antitumor effect of mIL-5 was completely abolished by subcutaneous injection of anti-mIL-5 monoclonal antibodies. The treatment of mice injected intraperitoneally with human IL-2 also resulted in an increase in survival. Winn assay experiments using PEC recovered from mIL-5-treated mice (1 microgram/day, from day -10 to -1) revealed that these PEC could mediate antitumor activity against Meth-A sarcoma cells. Furthermore, when the cured mice were re-injected with Meth-A sarcoma cells or syngeneic MOPC104E cells, they could reject Meth-A sarcoma cells but not MOPC104E cells, indicating that immune memory had been generated. These results suggest that IL-5 augmented the PEC tumoricidal activity but we have no indication that the tumoricidal activity was mediated through a mIL-5-dependent mechanism.

Effect of prostaglandin E2 on the chemiluminescence activity of peritoneal exudate cells of intact animals and animals inoculated with different materials

Effect of prostaglandin E2 on the chemiluminescence activity of peritoneal exudate cells of intact animals and animals inoculated with different materials

The characterization of peritoneal and pleural exudate cells from malignant effusions

The immune function of peripheral blood cells and cells from the pleural and abdominal effusions of patients with advanced cancer was compared to that of peripheral blood cells from controls. The parameters examined included lymphocyte subsets, natural killer (NK) cell activity, and anti-Daudi and lymphokine-activated killer (LAK) cell activity. The percentage of CD4+ pleural and peritoneal exudate cells (PEC) was significantly higher than the percentage of peripheral blood mononuclear cells (PBMC) in the patients. The percentage of CD8+CD11+ PEC and PBMC, being the suppressor T-cells, of the patients was increased compared with controls, while the percentage of CD8+CD11- PEC, being the cytotoxic T-cells, was identical to the PBMC of both patients and controls. The NK activity of PEC was significantly lower than that of PBMC in both patients and controls, and there was no correlation between the NK activity of PBMC and PEC. Although the anti-Daudi activity of PEC was markedly low, LAK cells with high activity could be induced by culture with interleukin-2 for 4 days. These results suggest that the immune function of cells in malignant effusions may be depressed due to a low population of cytotoxic T cells, low NK activity and increased suppressor T cells, while the local administration of interleukin-2 may induce LAK cells. Therefore, effective local immunotherapy for malignant effusions should not only augment effector cells, but also inhibit suppressor cells.

The induction of LAK cells in the peritoneal cavity of mice by combined treatment with OK-432 and rIL-2.

In ongoing studies on immunotherapy against peritoneal carcinomatosis, LAK cells were introduced into the peritoneal cavity of mice. Antitumor effects of i. p. treatments of OK-432 and rIL-2 given sequentially were studied. When OK-432 was given in a dose of 1 KE, the number of peritoneal exudate cells (PEC) and the ratio of asialo GM 1 (asGM 1)+ cells significantly increased in murine peritoneal cavity and a peak was reached on day 5 after treatment. The mice were then injected i. p. with rIL-2 at a dose of 5×104U. LAK activity of PEC against NK-resistant target cells, EL-4, on day 6 was significantly higher than that in case of PEC with OK-432 alone. In vivo pretreatment of the PEC with anti-asGM 1 antibody prior to rIL-2 eliminated the augmentation of LAK activity. Sequential injection of OK-432 and rIL-2 to mice bearing X 5563 plasmacytoma augmented the LAK activity of PEC and the survival rate of tumor bearing mice was increased. Thus, the in vivo induction of LAK cells by the combined sequential injection of OK-432 and rIL-2 may be given consideration for treating patients with peritoneal carcinomatosis.

The activation of rat peritoneal macrophages by 2,3,7,8-tetrachlorodibenzo-p-dioxin

The toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD] and its bioisosteres involves binding to a specific TCDD [Ah] receptor, interaction of this complex with chromatin, and the ultimate production of a pleiotropic response. We have hypothesized that TCDD toxicity also involves the production of oxidative stress [OS], and phagocytic cell activation may be a source of reactive oxygen species [ROS] following TCDD exposure. Evidence is provided for the activation of peritoneal exudate cells [PEC] following exposure of rats to TCDD. Increases of 2.5- and 3-fold in ROS production by PEC were observed 24 hrs following treatment of female Sprague-Dawley rats with a single dose of 50 μg TCDD/kg, utilizing the iodonitrotetrazolium and cytochrome c [cyt- c ] reduction assays, respectively. However, no increases in ROS production by isolated PEC were observed following in vitro incubation with 5, 25, 50, 100, 125 and 10,000 ng TCDD/ml of the assay medium using the nitroblue tetrazolium and cyt- c reduction assays. Phorbol myristate acetate was utilized as a positive control and resulted in a 3.5-fold increase in ROS production after a 15 min incubation with 3 × 10 6 PEC/ml at 37° C. PEC activation may contribute to OS following TCDD exposure, and the process may be receptor mediated.

Effects of swimming exercise on the pathogenesis of acute murine Toxoplasma gondii Me49 infection

The effects of swimming exercise on the pathogenesis of acute murine toxoplasma infection were studied. Swimming (45 min/day) initiated on the day of inoculation with the avirulent Me49 strain of Toxoplasma gondii did not alter survival of infected mice. At a later stage of infection, daily swimming appeared to promote the recovery of appetite and weight gain. Immune activation was apparent in toxoplasma-infected mice, and swimming blunted splenic enlargement but not the respiratory burst activity of peritoneal exudate cells. Infection caused a significant elevation of serum tumor necrosis factor (TNF) levels which was attenuated by a daily swimming program. These data show that swimming exercise is not deleterious to mice acutely infected with T. gondii Me49 and that the more rapid recovery in exercised mice is associated with reduced serum TNF levels.

Effects of protein intake on immune parameters in mice surviving streptococcal infection.

Groups of mice were fed for 2 weeks on isocaloric diets containing 5, 7, 20 and 40% (w/w) casein, respectively, then injected intraperitoneally with group B streptococci, and observed for their survival rates. The mice fed 7% or 20% casein had lower mortalities than those fed 5% or 40% casein. In order to explain the different survival rates, other groups of mice were fed on the experimental diets and examined for the number of leukocytes in the blood, of spleen cells and thymocytes, for IgG and IgM antibody titres to the streptococci, for haemolytic titres of sera, the amount of complement component 3 (C3), for chemiluminescence and opsonic activity of peritoneal exudate cells (PEC) and spleen cells (SP), production of superoxide anion from PEC and SP, and production of immunoglobulins from cultured SP. After 2 weeks on a 7 or 20% casein diet mice showed increased serum levels of IgM antibodies reactive with the whole bacterial cells on days 3-5 when they were immunised with a sublethal dose of group B streptococci. The mice fed on the 7% casein diet also showed a higher C3 titre than the other diet groups when assayed by enzyme immunoassay. Furthermore, opsonophagocytic activity was highest when PEC or SP taken from mice on the 20% case in diet were incubated with radiolabelled microorganisms in the presence of fresh serum taken from the 7% casein group. The production of superoxide anions from PEC and SP was lowest in the mice fed on 5% casein when activity was expressed as nano-mol per animal. It is suggested from these results that the greater activity of phagocytic cells in the presence of increased amounts of C3 and IgM explains the heightened resistance in the mice fed on a 7% casein diet, and that suppressed opsonophagocytic activity resulting from the decreased number of leukocytes in the blood and other phagocytic cells explains the lowest resistance in the 5% casein group. However, mice fed on a 40% casein diet showed all these immunological parameters untouched, and their lowered resistance could not be explained. Different factors seem to be operative in them.

Effects of protein intake on immune parameters in mice surviving streptococcal infection

Groups of mice were fed for 2 weeks on isocaloric diets containing 5, 7, 20 and 40% (w/w) casein, respectively, then injected intraperitoneally with group B streptococci, and observed for their survival rates. The mice fed 7% or 20% casein had lower mortalities than those fed 5% or 40% casein. In order to explain the different survival rates, other groups of mice were fed on the experimental diets and examined for the number of leukocytes in the blood, of spleen cells and thymocytes, for IgG and IgM antibody titres to the streptococci, for haemolytic titres of sera, the amount of complement component 3 (C3), for chemiluminescence and opsonic activity of peritoneal exudate cells (PEC) and spleen cells (SP), production of superoxide anion from PEC and SP, and production of immunoglobulins from cultured SP. After 2 weeks on a 7 or 20% casein diet mice showed increased serum levels of IgM antibodies reactive with the whole bacterial cells on days 3–5 when they were immunised with a sublethal dose of group B streptococci. The mice fed on the 7% casein diet also showed a higher C3 titre than the other diet groups when assayed by enzyme immunoassay. Furthermore, opsonophagocytic activity was highest when PEC or SP taken from mice on the 20% case in diet were incubated with radiolabelled microorganisms in the presence of fresh serum taken from the 7% casein group. The production of superoxide anions from PEC and SP was lowest in the mice fed on 5% casein when activity was expressed as nano-mol per animal. It is suggested from these results that the greater activity of phagocytic cells in the presence of increased amounts of C3 and IgM explains the heightened resistance in the mice fed on a 7% casein diet, and that suppressed opsonophagocytic activity resulting from the decreased number of leukocytes in the blood and other phagocytic cells explains the lowest resistance in the 5% casein group. However, mice fed on a 40% casein diet showed all these immunological parameters untouched, and their lowered resistance could not be explained. Different factors seem to be operative in them.

Failure of dietary restriction to enhance cytolytic and chemiluminescent activity of peritoneal exudate cells from ageing rats

Investigations into the cytolytic activity of peritoneal macrophages from male Sprague-Dawley rats (activated in vivo with Corynebacterium parvum) utilised SV40-3T3 and L-929 target cells in a 72 h [ 3H]thymidine release assay. The dietary restricted rats under test were given a measured amount of food from weaning sufficient to maintain their body weights at approximately 50% of age-matched controls fed ad libitum. Cytolytic activity was similar in the two dietary groups at both 13 and 21 months of age, nor were chemiluminescent responses of peritoneal cells to latex or zymosan particles affected by the dietary restriction. No differences were seen in the effectiveness of zymosan particles opsonised with serum pooled from dietary restricted versus control rats in stimulating chemiluminescent responses by standard preparations of peritoneal cells, and concentrations of serum C3 and IgG appeared to be unchanged by the dietary regime.

Cyclophosphamide modifies the induction kinetics but not cell types and cytotoxic mechanisms of antitumor cells elicited with OK-432 plus attenuated tumor cells.

The present study was designed to examine whether the antitumor cells induced by treatment with mitomycin-C-treated EL4 cells (EL4MMC) plus OK-432 plus cyclophosphamide differed from those induced by treatment with EL4MMC plus OK-432 in terms of their cell types and antitumor mechanisms. Antitumor activity of peritoneal exudate cells (PEC) from mice receiving either treatment was nonspecific, and inhibition of their target cell growth increased for up to 24 h. Macrophage toxin, silica and trypan blue abrogated the activity in vitro and in vivo, respectively. The activity of the PEC was inhibited with inhibitors of the arachidonic acid cascade, such as dexamethasone, 4-bromophenacyl bromide and nordihydroguaiaretic acid but not esculetin, ibuprofen, indomethacin and BW755C. NG-monomethyl-L-arginine, a specific competitive inhibitor of the L-arginine-dependent nitric oxide synthesis, also inhibited the activity. These results and morphological observations indicated that antitumor cells in the PEC from mice receiving either treatment were macrophages, and that their activity was closely related to the arachidonic acid cascade and to nitric oxide. Antitumor activity of the PEC spontaneously decayed in vitro and this decay was inhibited by the addition of OK-432 or lipopolysaccharide. On the other hand, cyclophosphamide sustained the appearance of antitumor cells in mice treated with EL4MMC plus OK-432. Therefore, cyclophosphamide treatment did not modify cell types and cytotoxic mechanisms of antitumor cells elicited with EL4MMC plus OK-432, but did modify the induction kinetics of such antitumor macrophages.

Effects of immobilization stress on the pathogenesis of acute murine toxoplasmosis

Stress modulates a variety of immune responses. We investigated the effects of immobilization stress on the pathogenesis of acute murine toxoplasmosis, an infection in which cell-mediated immunity is of major importance in host defense. Repetitive over-night immobilization beginning 3 days prior to infection enhanced ( p < 0.05) the mortality of mice infected with a virulent strain (C56) of Toxoplasma gondii (77% vs 15% mortality in restrained and control mice, respectively). Daily immobilization for 14 days prior to infection abrogated ( p < 0.05) the lethal effect of immobilization, suggesting an adaptive mechanism. To explore the effect of immobilization with a less virulent strain, the Me49 strain of T. gondii was studied. Acute infection with T. gondii Me49 resulted in anorexia and weight loss, while spleen size and respiratory burst activity of peritoneal exudate cells were enhanced ( p < 0.01). Immobilization (twice daily for 2 h) did not significantly alter survival or other clinical features of acute T. gondii infection. In addition, immobilization suppressed ( p < 0.05) phorbol myristate acetate-stimulated release of superoxide anion by peritoneal exudate cells in healthy naive mice, but not in infected mice. These findings indicate that immobilization stress can alter the pathogenesis of acute T. gondii infection in healthy mice, but the effect of this stress paradigm will be influenced, in part, by the timing of the immobilization and the virulence of the strain of T. gondii.

Induction of tumor cytotoxic immune cells using a protein from the bitter melon ( Momordica charantia)

The fruit and seeds of the bitter melon ( Momordica charantia) have been reported to have anti-leukemic and antiviral activities. This anti-leukemic and antiviral action was associated with an activation of murine lymphocytes. A partially purified protein factor from the bitter melon caused an infiltration and activation of peritoneal exudate cells in C57B1/6J, C3H/HeJ, and C3H/HeN mice. When the extract was injected twice a week at 8 μg of protein per ip injection for 0–4 weeks, the peritoneal exudate cells from the treated mice were cytotoxic in a long-term (18-hr) 51Cr-release assay against a range of labeled targets; L1210, P388, and MOLT-4 tumor cells. Cytotoxicity was also observed against YAC-1 targets in a short-term (4-hr) assay. Fractionation of the cytotoxic immune cells implicated a nonadherent cell population which was capable of killing an NK-sensitive cell line in a 4-hr 51Cr-release assay. Unit gravity sedimentation studies indicated that the cytotoxicity was due to either a neutrophil or a large lymphocyte. Antibody depletion experiments using antibody to asialo GM1, an NK cell-specific antibody, depleted cytotoxicity observed in nonadherent, Ficoll/Hypaque-separated PEC. This suggests that at least part of the anti-leukemic activity of the bitter melon extract is due to the activation of NK cells in the host mouse.

Protection of OK‐432, a Streptococcus pyogenes Preparation, against Lethal Infection of Mice with Herpes Simplex Virus

We have studied the protective effect of OK-432, a biological response modifier (BRM) of Streptococcus pyogenes origin, on the lethal infection of mice with herpes simplex virus (HSV)-1. A single intraperitoneal (i.p.) injection of more than 10 micrograms of OK-432, when given at least two days before the infection, gave a marked effect yielding nearly 100% protection against ordinarily lethal infection. The protection was independent of the amount of infected virus inoculated. When given after the infection, the agent even at the maximal dose (100 micrograms), produced only a marginal effect. A single i.p. administration of OK-432 augmented the natural killer (NK) activity of peritoneal exudate cells and spleen mononuclear cells in mice 2 to 3 days after injection of OK-432, coinciding with the times when it induced a survival effect on HSV-infection. Treating OK-432-treated mice with a combination of an anti-macrophage agent, silica, and an anti-NK cell agent, anti-asialo GM1 serum, before infection diminished the antiviral effect of OK-432. The OK-432 protection against HSV infection was also markedly diminished in athymic nude mice. Thus, the protective effect of OK-432 on lethal HSV infection seems to be based on the activation of NK cells, macrophages, and T lymphocytes.

Selenium and the Immune Response: 2. Enhancement of Murine Cytotoxic T-Lymphocyte and Natural Killer Cell Cytotoxicity In Vivo

An inverse correlation between cancer incidence and dietary intake of the trace mineral element selenium has been well established in epidemiological and experimental studies. The mechanisms for this chemoprotective effect are unresolved. Much attention has been focused on the antiproliferative effects of selenium on various normal and neoplastic cell types. However, dietary selenium supplementation can also enhance the expression of various humoral and cellular immune responses. In examining the effects of dietary selenium on cell-mediated immunity in mice, we observed that selenium supplementation caused the enhanced expression of spontaneous natural killer (NK) cytotoxicity in spleen cells and of specific cytotoxic T-lymphocyte (CTL) cytotoxicity in peritoneal exudate cells (PEC). NK activity of spleen-cell suspensions from selenium-supplemented mice increased an average of 70% over that of the control group (basal diet). Cytotoxic activity of PEC from mice injected with tumors intraperitoneally peaked earlier in selenium-supplemented animals, and the appearance of cells staining positively for Thy 1.2 surface antigen in selenium-supplemented animals also preceded the values observed in control animals. We propose here that enhancement of in vivo cytotoxic mechanisms, is likely to act synergistically with tumor growth inhibition in the reduction of tumor incidence associated with selenium intake.

Enhancement of in vitro cytotoxicity of mouse peritoneal exudate cells by flavone acetic acid (NSC 347512)

Flavone acetic acid (FAA), an antitumour agent currently undergoing clinical trials, was found to augment the tumoricidal activity of peritoneal exudate (PE) cells in vitro. Lysis of tumour targets was measured using a standard 18 h 51Cr release assay for activated macrophages. Lytic activity increased with increasing concentrations of FAA up to 100 μg/ml before reaching a plateau. At 80 μg/ml FAA, 3-fold fever PE cells were necessary to obtain the same level of activity as in control cultures without FAA. The lytic activity was mediated by Thy- 1 negative and glass-adherent cells in the PE population, and was inhibited by dexamethasone. The activity of PE cells against several different tumour targets (P815 mastocytoma, YAC- 1 lymphoma, P 388 lymphoma, and a Lewis lung carcinoma cell line) were all enhanced by FAA. The results show that FAA can enhance the lytic potential of peritoneal macrophages in vitro to kill a range of tumour cells.