In vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappa

We investigated in vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone from Saussurea lappa, on tumor necrosis factor (TNF)-alpha and nitric oxide (NO) release, and lymphocyte proliferation. Cynaropicrin strongly inhibited TNF-alpha release from lipopolysaccharide-stimulated murine macrophage, RAW264.7 cells, and differentiated human macrophage, U937 cells, proved to produce notable amount of TNF-alpha. It also potently attenuated the accumulation of NO released from lipopolysaccharide- and interferon-gamma-stimulated RAW264.7 cells in a dose-dependent manner. In addition, the immunosuppressive effects of the compound on lymphocyte proliferation in response to mitogenic stimuli were examined. Cynaropicrin also dose-dependently suppressed the proliferation of lymphocytes from splenocytes and interleukin-2-sensitive cytotoxic T lymphocyte, CTLL-2 cells, stimulated by lipopolysaccharide, concanavalin A, phytohemagglutinin and interleukin-2. However, treatment with sulphydryl compound, L-cysteine, abrogated all these inhibitory effects. These results suggest that cynaropicrin may participate in the inflammatory response by inhibiting the production of inflammatory mediators and the proliferation of lymphocytes and its inhibitory effect is mediated through conjugation with sulphydryl groups of target protein(s).     

Suppressive effects of chlorphenesin on lymphocyte function in mice and humans.

The immunosuppressive action of chlorphenesin was investigated in a wide variety of in vitro assays for cellular immunity in humans and mice. Chlorphenesin, at doses of 20-50 micrograms/ml, inhibited mitogenic responses of both mouse and human B and T cells. These doses did not kill cells exposed to the drug for 72 hr. Mixed lymphocyte reactions in inbred strains of mice and in unrelated humans were also inhibited at concentrations of about 50 micrograms/ml. However, the generation of cytotoxic T cells in cell-mediated lympholysis assays was not inhibited to the same degree as proliferation in mixed lymphocyte reaction and the cytotoxic potential of presensitized mouse T cells for allogeneic targets was totally unaffected. These studies suggest that chlorphenesin may have a broad spectrum of suppressive effects both on T and B cells and that the predominant inhibition of proliferative responses in these cells may reduce the expansion of clones of immunocompetent cells in vivo.     

Decreased lymphocyte blastogenesis,IL2 production and NK activity following nifedipine administration to healthy humans

Summary The effects of a single oral dose of nifedipine on part of the immune response in healthy humans has been investigated in terms of two different immune functions: T lymphocyte proliferation and NK activity. Both functions are known to require calcium ions.Ten healthy subjects were bled before and 30 min, and 4 and 24 h after receiving 10 mg nifedipine. Lymphocyte proliferation, both in mitogen-activated lymphocyte cultures, and in autologous and allogeneic mixed lymphocyte reactions, was significantly reduced (up to 48%) 30 min after drug administration and reverted to normal 4 h later. The inhibition could be attributed to reduction in IL2 production by the T cells isolated 30 min following the administration of nifedipine, since they normally express IL2-receptors. The addition of recombinant IL2 of 200 U·ml^–1 to the cell cultures restored their responsiveness.NK activity was significantly reduced 30 min and 4 h after drug administration and returned to normal at the 24th h. This function was also restored by the addition of IL2.The data suggest that calcium channel blockers may inhibit, at least transiently, lymphocyte functions in vivo.List of abbreviations AMLC Autologous mixed lymphocyte cultures - CD Cluster determinants - ConA Concanavallin A - CTL Cytotoxic T lymphocytes - GAM-FITC Fluorescein isothiocyanate-conjugated goat anti-mouse immunoglobulins - HLA-class II DP-DQ-DR antigens - IL2 Interleukin 2 - mAb Monoclonal antibodies - MHC Major histocompatibility gene complex - MLC Mixed lymphocyte cultures - NK Natural killer activity - non- T/T type AMLC Autologous mixed lymphocyte culture in which non-T cells are used as stimulators - PBL Peripheral blood lymphocytes - T/T type AMLC Autologous mixed lymphocyte culture in which PHA-activated T lymphocytes are used as stimulators     

The effects of immunosuppressive pharmacological agents on the induction of cytotoxic and suppressor T lymphocytes in vitro

The immune system is regulated by the interactions among several distinct functional subsets of T cells. The action of several commonly used immunosuppressive drugs on the activation of cytotoxic T lymphocytes (CTL) and suppressor T lymphocytes (Ts) in the primary mixed lymphocyte reaction (MLR) was investigated. Cyclosporin A, hydrocortisone, and azathioprine were all found to inhibit both CTL and Ts activation when present at pharmacological doses in culture. When these drug-inhibited cultures were reconstituted with interleukin-2, however, clear differences between the effects of these drugs was observed. Cyclosporin A and hydrocortisone allowed the selective activation of Ts in the presence of interleukin-2, while azathioprine inhibition was not reversed by interleukin-2. Thus, CTL precursors appear to be directly inhibited by all of these drugs, but Ts precursors apparently are not inhibited by cyclosporin A or hydrocortisone provided interleukin-2 is present. These findings are discussed in terms of the activation requirements of CTL vs. Ts and the implications of the selective activation of alloantigen-specific Ts for prevention of allograft rejection.     

Immunotoxicity of N,N-diethylaniline in mice: effect on natural killer activity, cytotoxic T lymphocyte activity, lymphocyte proliferation response and cellular components of the spleen

We previously found that N,N-diethylaniline increased the frequency of sister chromatid exchange (SCE) of human lymphocytes to about five times that of the control value, and was as toxic as cyclophosphamide used as a positive control for SCE. To explore whether N,N-diethylaniline affects the function of lymphocytes, we evaluated its immunotoxicity using CBA/N mice. The mice were divided into four groups and received 0, 100, 200, or 400 mg/kg body weight of N,N-diethylaniline by subcutaneous injection. The following items were investigated on days 3 and 7 after injection: body weight, weight of spleen, number of splenocytes, natural killer (NK) and cytotoxic T lymphocyte (CTL) activities, and concanavalin A (Con A)- and lipopolysaccharide (LPS)-stimulated lymphocyte proliferation using splenocytes. The following splenocyte phenotypes were also quantified by flow cytometry: (1) B cells; (2) total T cells; (3) CD4⁺ and CD8⁺ T cells; (4) NK; (5) macrophages and (6) nucleated erythrocytes. The splenic NK and CTL activities in exposed groups significantly decreased compared to the control in a dose-dependent manner and lymphocytes from the 200 and 400 mg/kg groups showed significantly higher spontaneous proliferation. The weight of the spleen and number of splenocytes were significantly higher in exposed groups than in the control. N,N-Diethylaniline also increased the percentages of macrophages, nucleated erythrocytes and B cells in the spleen. On the other hand, N,N-diethylaniline did not affect LPS-stimulated B cell and Con A-stimulated T cell proliferation, or the percentages of NK, total T, and CD4⁺ and CD8⁺ T cells in the spleen or the body weight of mice. The above findings indicated that N,N-diethylaniline selectively inhibited splenic NK and CTL activity and this inhibition was due to decreased NK and CTL functions, but not due to changes in the numbers of splenic NK and T cells.     

新城疫病毒疫苗及白细胞介素-15对卵巢癌细胞株体外作用的实验研究

目的研究新城疫病毒疫苗（ATV—NDV）和白细胞介素-15（IL-15）对人卵巢癌细胞株体外生长的作用。方法将正常人卵巢上皮细胞和人卵巢癌细胞株3AO体外培养;分离正常人外周血淋巴细胞;制备人卵巢癌细胞株3AO ATV-NDV,（1-2）×10^7细胞／0．5ml;将ATV—NDV、IL-15、ATV—NDV＋IL-15分别与正常人外周血淋巴细胞共培养24、48、72、96小时;用正常人外周血淋巴细胞作对照,用MTT比色法测定不同浓度ATV-NDV、IL-15作用不同时间对淋巴细胞增殖程度的影响,将ATV-NDV（50μl）、rhIL-15（50ng／ml）及ATV-NDV（50μl）＋IL-15（50ng／ml）与人外周血淋巴细胞共培养48小时,按效靶比分别为50：1、25：1、10：1加入正常人卵巢上皮细胞和人卵巢癌细胞株3AO,继续培养24、48、72、96小时,MTT法测定细胞生长抑制率;HE染色法观察效靶比为50：1、继续培养24—96小时后细胞形态学变化。结果1．淋巴细胞增殖改变：ATV—NDV、IL-15具有对淋巴细胞的增殖活性,随浓度的增加和时间的延长而增强（P〈0．05）,与对照组相比差异有显著性（P〈0．01）。IL-15与ATV—NDV具有协同作用,并且这种协同作用与IL-15、ATV-NDV的单独作用相比差异有显著性（P〈0．01）;IL-15、ATV—NDV对正常人外周血淋巴细胞增殖作用的影响与对照组相比差异有显著性（P〈0．01）;IL-15与ATV-NDV作用相比差异无显著性（P=0．35）。2．ATV-NDV、IL-15对肿瘤细胞生长抑制作用：活化的淋巴细胞与靶细胞共培养可杀死肿瘤细胞,并具有时效性（P〈0．05）。3．细胞形态学变化：活化的淋巴细胞作用48小时后肿瘤细胞即已出现凋亡形态,作用96小时时即有坏死细胞形态出现。结论ATV—NDV和IL-15对正常人外周血淋巴细胞增殖有影响,经ATV-NDV、IL-15及ATV—NDV＋IL-15共培养的正常人外周血淋巴细胞可有效地抑制细胞株3AO生长,具有时间、浓度依赖性。     

Immunosuppressive properties of chloroquinoxaline sulfonamide

Chloroquinoxaline sulfonamide (CQS), a sulfanilamide derivative with antitumor activity, was found to be toxic to lymphoid tissue during preclinical studies. The mechanism of this toxicity appears to involve profound inhibition of lymphocyte activation. Incubation of human peripheral blood mononuclear cells (PBMNCs) with CQS decreased cellular incorporation of thymidine and deoxyuridine in a dose-dependent manner. Analysis of cell cycle distribution by flow cytometry indicated that CQS blocked movement out of the G0/G1 phase. Drug-treated cells were smaller and expressed fewer receptors for interleukin-2 (IL-2) and transferrin than untreated mitogen-stimulated lymphocytes. These observations support the notion that CQS has cell cycle specificity in regulating lymphocyte proliferation. As little as 10 microM CQS markedly inhibited both human lymphocyte and murine CTLL cell replication in response to IL-2 containing growth factors. However, CQS did not block secretion of IL-2 into culture supernatant fractions by human PBMNCs. Finally, CQS inhibited in vitro production of immunoglobulins G and M by mitogen-stimulated lymphocytes, primarily by causing cytotoxicity. In all of these drug effects, CQS was approximately one to two logs more potent than the parent compound, sulfaquinoxaline (SQ). These studies indicate that CQS inhibits essential basic processes in human lymphocytes. This agent may find use as an immunosuppressive drug.     

Organophosphorus pesticide immunotoxicity: effects of O,O,S-trimethyl phosphorothioate on cellular and humoral immune response systems

The time course of immunosuppression induced by acute treatment with O,O,S-trimethyl phosphorothioate (OOS-TMP), an impurity in technical formulations of malathion, was examined in female C57B1/6 mice. Both cell-mediated and humoral immune responses were examined and included allospecific cytotoxic T cells, proliferative response to mitogens, interleukin-2 production and antibody production to sheep red blood cells. OOS-TMP pretreatment led to a reversible suppression of the generation of cytotoxic T lymphocytes and antibody-secreting cells to sheep erythrocytes. However, the mitogenic response of splenocytes from animals treated with nontoxic doses of OOS-TMP (as measured by body weight loss, serum cholinesterase levels and splenic lymphocyte number) to concanavalin A was not significantly suppressed, but the response to the B cell mitogen lipopolysaccharide was slightly decreased on day 1 following treatment. In contrast, interleukin-2 production was elevated by 24 h following treatment, but had returned to control levels by day 7. These data suggest that OOS-TMP was able to block the generation of cytotoxic T lymphocytes and antibody responses at doses of OOS-TMP that did not affect body weight or splenic lymphocyte number and this suppression was reversible.     

Inhibitory effect of deoxynivalenol, 3-acetyldeoxynivalenol and zearalenone on induction of rat and human lymphocyte proliferation

Deoxynivalenol (DON), 3-acetyldeoxynivalenol (acetylDON) and zearalenone (Ze) were examined for their in vitro effect on mitogen-induced lymphocyte blastogenesis using rat or human peripheral blood lymphocytes (PBL). A dose-dependent reduction of lymphocyte proliferation was demonstrated for each mycotoxin. However, the inhibitory effect of DON was significantly higher than that of the acetylated compound. Concentrations of 90 ng/ml and 220 ng/ml inhibited rat and human lymphocyte blastogenesis by 50%, respectively, whereas 450 ng/ml and 1060 ng/ml acetylDON were required to produce the same effect. The amount of Ze necessary to inhibit blastogenesis by 50% was 250 times greater than required for DON. There was no evidence of cell death and combinations of DON and Ze did not alter the expected response.     

Modulation of in vitro immune reactions by platelet activating factor and a platelet activating factor antagonist

Platelet activating factor (PAF) was found to suppress primary and secondary mixed lymphocyte reactions and BN52021, a naturally occurring PAF antagonist, blocked PAF-mediated suppression and enhanced the mixed lymphocyte reactions. The effect of delayed addition of PAF or BN52021 24 h or later after the initiation of cultures reduced the suppressive and enhancing effects, respectively. The removal of the antagonist BN52021 from mixed lymphocyte cultures up to 72 h after their initiation also was found to eliminate the potentiating effect of this antagonist. The continuous presence of PAF in mixed lymphocyte cultures used to generate cytotoxic lymphocytes suppressed the generation of effector cells while the addition of BN52021 elicited an enhanced level of cell-mediated cytotoxicity in such cultures. BN52021 enhanced the cytotoxic activity in such cultures irrespective of the presence of exogenous interleukin-2, suggesting that the antagonist-mediated enhancement is not due to the enhanced production of interleukin-2 by cells in the mixed cultures. The experiments reported here provide evidence for a role of PAF in modulating the complex interactions that take place in the initiation of cellular immune reactions. Furthermore, the results of these experiments indicate that the immunoregulatory action of PAF can be modulated by an antagonist that exerts its action independently of the production of the lymphocyte growth factor, interleukin-2.     

螺旋藻多糖硫酸酯化修饰前后抗肿瘤及免疫活性的研究

比较螺旋藻多糖硫酸酯化修饰前后体内外抗肿瘤及免疫活性.采用MTT比色法研究药物在体外对人肿瘤细胞株的抑制作用,促进正常小鼠脾淋巴细胞的增殖活性以及对荷瘤小鼠NK和CTL细胞活性的影响.采用移植性肿瘤实验方法考察了药物对小鼠S180肉瘤的抑制作用.结果显示,螺旋藻多糖（NPSP）对肿瘤细胞株几乎无细胞毒作用,硫酸酯化螺旋藻多糖（SNPSP）对肿瘤细胞株具有显著的细胞毒作用,其中对SMMC-7721人肝癌细胞株抑制率最高达50%.NPSP50 mg/kg对小鼠S180肉瘤无抑制,相同剂量的SNPSP对小鼠S180肉瘤的抑制率达35.42%.NPSP具有促进脾淋巴细胞增殖作用,但对ConA和LPS诱导的脾淋巴细胞增殖反应无促进作用,SNPSP促进脾淋巴细胞增殖作用较NPSP增强,同时对ConA和LPS诱导的脾淋巴细胞增殖反应也具有明显的促进作用.NPSP和SNPSP均能促进荷瘤小鼠NK细胞和CTL细胞活性,其中SNPSP促进CTL细胞活性较NPSP增强.     

Modulation of murine in vitro immune response by verapamil (V)

Functionally distinct lymphocyte subsets differ with regard to necessary activation signals. In selected circumstances lymphocyte activation has been shown to be critically dependent upon transcellular calcium influx. Whether calcium plays a central role in the activation of all lymphocytes remains to be determined. The effect of the calcium channel blocker verapamil on the induction of murine cytotoxic T lymphocytes (CTL), suppressor cells, T helper cells, and B cells was investigated. Verapamil (V) was found to inhibit the induction of cytotoxic effector cells. V acted primarily on the afferent limb of this immune response, was synergistic with cyclosporin A (CsA), and its effects could be largely reversed by the addition of exogenous helper factors. V also inhibited B cell proliferation in response to anti-mouse IgM in the presence of 2-mercaptoethanol, but in the absence of cognate or non-cognate T cell help. In contrast to this, V did not inhibit the activation of cells capable of inducing B cell proliferation nor did it inhibit the induction of suppressor cells. The selective suppression of V is discussed in terms of activation requirements of CTL, suppressor cells and helper cell subsets.     

Interpretation of lymphocytotoxicity assays and the demonstration of auto-tumor reactive lymphocytes in patients: central issues of present day tumor immunology

The outcome of a short term cell-mediated cytotoxic assay depends on the susceptibility of the target and the activation profile of the lymphocyte population. Certain cultured cell lines are highly sensitive to the lytic effect of lymphocytes of unimmunized donors, provided they have been derived from the same species--NK effect. This cytotoxicity seems to be independent of lymphocyte receptor-target antigen interaction but is likely due to some membrane property of the target. Specificity is only on the species level. With fresh, non-cultured targets, in certain systems which operationally conform with the natural killing henomenon, antigen specific recognition defines the effect. We propose that on fresh targets, the operational NK effect, should be viewed fundamentally similar to CTL. Analysis of antigen induced cytotoxic systems suggests that the question of "specificity" on the effector level can only be asked if target cells of similar characteristics are used. Specificity at the effector level depends on the panel of targets presented. Cells with inherent sensitivity to the lytic effect of activated lymphocytes (i.e. NK sensitive cells) may be killed even if they are unrelated to the stimulus, and also such NK resistant cells which carry antigens for which the relevant receptor carrying lymphocytes are present in a sufficient number. Lysis of the latter cells can occur due to transactivation. Transactivation means that accompanying the event of antigen specific recognition in a lymphocyte population, additional cells are activated that do not participate in the specific reaction. In patients with solid tumors lymphocytes which recognize autologous tumor biopsy cells and can damage them, have been demonstrated. Auto-tumor-killer lymphocytes have been generated in conventional mixed lymphocyte cultures, using the patient's lymphocytes as responders--probably due to transactivation or in mixed lymphocyte cultures containing lymphocytes and autologous tumor cells.     

The inhibitory effect of phenothiazines on NK-mediated cytolysis of tumor cells

Non-toxic concentrations of fluphenazine caused a marked (90%) inhibition of NK-mediated cytolysis of YAC-1 tumor cells. The biologically inactive sulphoxide derivative was not inhibitory and the efficacy of inhibition of other compounds was directly correlated (r = -0.96, p less than 0.02) with their reported affinities for calmodulin. Fluphenazine may act on the earliest stages of the target-effector interaction since conjugate formation between CBA effectors and YAC target cells decreased from 20% to 6% (p less than 0.02) upon pre-treatment with fluphenazine. However, fluphenazine was not selective for NK cells since cytotoxic T lymphocytes, derived from both mixed lymphocyte culture and by concanavalin A stimulation, revealed depressed cytolytic activity against P815 tumor targets after fluphenazine treatment. Tumoricidal activity by activated macrophages and effectors of antibody-dependent cell-mediated cytotoxicity was also blocked. Fluphenazine inhibition was reversible, since addition of 1.25-5 micrograms/ml of the calcium ionophore A23187 to fluphenazine-treated effectors restored NK binding and cytolytic functions to normal levels. Calmodulin was isolated from NK-enriched populations by affinity chromatography on sepharose-fluphenazine columns. Pre-treatment of effector cells with [3H]fluphenazine and isolation of calmodulin by immunoprecipitation and SDS-polyacrylamide gel electrophoresis showed that fluphenazine entered the cells and bound a calmodulin-like molecule. These data are compatible with the suggestion that fluphenazine inhibits NK function by inactivating the calcium-calmodulin complex and thereby altering binding events in the target-effector interaction. Other actions of the phenothiazines are also possible.     

白芷提取物对大鼠脾淋巴细胞免疫抑制作用初探

目的探讨白芷提取物对地塞米松致大鼠脾淋巴细胞免疫抑制作用的影响。方法建立地塞米松致大鼠免疫抑制模型,考察白芷提取物对大鼠脾淋巴细胞的增殖活性、自然杀伤细胞（NK细胞）活性的影响。结果白芷提取物（5．0g/kg）对刀豆蛋白A（ConA）诱导脾淋巴T细胞增殖能力有升高作用,但对脂多糖（LPS）诱导脾淋巴B细胞增殖能力未见明显影响,对脾淋巴细胞的NK细胞活性也有增强作用。结论白芷提取物（5．0g／kg）曲能提高大鼠脾淋巴T细胞和NK细胞的增殖活性。     

当归多糖组分AP-3对不同淋巴细胞亚群的作用

目的观察当归多糖组分AP-3对不同淋巴细胞亚群的作用。方法免疫磁珠法制备T、B细胞亚群;四甲基偶氮唑蓝(MTT)法检测细胞增殖;流式细胞术观察CD4+T细胞亚群比例的变化。结果在30~300μg/ml范围内,AP-3能显著促进小鼠脾淋巴细胞、巨噬细胞、混合淋巴细胞和T淋巴细胞的增殖反应,而对B细胞增殖有一定的抑制作用;显著增加培养的脾细胞中CD4+T细胞亚群的比例。结论当归多糖具有独特的免疫调节特性,活化巨噬细胞、T细胞以及辅助性T细胞(Th细胞),但对B细胞有一定的抑制作用。     

Investigations into the mechanism of immunosuppression caused by acute treatment with O,O,S-trimethyl phosphorothioate. II. Effect on the ability of murine macrophages to present antigen

Acute administration of 10 mg/kg O,O,S-trimethyl phosphorothioate (OOS-TMP) for 24 h has been shown to suppress the in vitro generation of cytotoxic T lymphocyte responses and antibody-secreting cells to sheep red blood cells and to increase interleukin-2 production. Macrophages were shown to be the splenic cell population most affected by OOS-TMP pretreatment. In this report, the ability of macrophages from OOS-TMP-treated animals to function in antigen presentation was shown to be significantly decreased. In addition, macrophages from treated animals had increased phagocytic capability and interleukin-l production. However, the percentage of Ia-positive macrophages present in splenic populations was decreased following OOS-TMP treatment. A decrease in antigen presenting ability and the number of Ia-positive macrophages may explain the reversible suppression in cytotoxic T lymphocytes and antibody responses reported previously.     

PCP and analogs prevent the proliferative response of T lymphocytes by lowering IL2 production. An effect related to the blockade of mitogen-triggered enhancement of free cytosolic calcium concentration

The psychotomimetic drug PCP displays a vast array of known pharmacological effects, among them its capacity to affect cation transport in nervous and myocardiac tissues. Since increased movements of cations are essential for the immune responses, it has been mentioned that PCP could also depress immune functions by this mechanism. In order to check this hypothesis, we have investigated the effects of PCP and of many other structural derivatives on the blastogenic response of murine or human T lymphocytes. We find that all the drugs block an early event of T lymphocyte activation and prevent their further proliferation; conversely they do not affect primed lymphocytes. The compounds, which do not inhibit interleukin-1 (IL-1) production in stimulated macrophages, lower interleukin-2 (IL-2) synthesis in activated T helper cells. This negative action appears to be related to the inhibition of the rise of free cytosolic calcium concentration [Ca2+]i observed soon after the T receptor triggering and which is an essential message for IL-2 production. The lymphocyte membrane depolarization induced by the drugs could explain the blockade of the lectin-induced [Ca2+]i changes. The study of the structure-activity relationship shows that the PCP analogs which possess a quasi-rigid conformational structure express an inhibitory capacity of T lymphocyte proliferation higher than that of PCP (200 times for some products). Since these compounds interact poorly with the CNS tissues and have few behavioral effects, we suggest that PCP exerts its negative action on lymphocytes on cell components different from its receptor(s) in the CNS.     

Effects of mycotoxins on human immune functions in vitro.

Immunosuppressive and carcinogenic Fusarium mycotoxins may appear in domestic food products. Therefore, the immunological effects of Fusarium mycotoxins were tested on human peripheral blood mononuclear cells from different blood donors. In the present study we investigated deoxynivalenol (DON), 3-acetyldeoxynivalenol, fusarenon-X, T-2 toxin, zearalenone, alpha-zearalenol, beta-zearalenol and nivalenol for their effects on T and B cells in a proliferation assay, antibody-dependent cellular cytotoxicity (ADCC) and natural killer (NK) cell activity on human peripheral blood mononuclear cells. The concentrations applied in our experiments were similar to those which can be found in normal human peripheral blood system (0.2--1800 ng/ml). Among the eight mycotoxins tested, T-2 toxin, fusarenon X, nivalenol and deoxynivalenol exerted the highest immunosuppressing effect on human peripheral blood mononuclear cells in vitro. Mycotoxin-induced immunosupression was manifested as depressed T or B lymphocyte activity. Furthermore, by virtue of inhibition of NK cell activity, the protection against tumor development may also be attenuated.