Blastogenesis Of Peripheral Blood Mononuclear Cells Research Articles

Suppressive potencies of calcineurin inhibitors against the mitogen-induced blastogenesis of peripheral-blood mononuclear cells of myasthenia gravis patients

Abstract The calcineurin inhibitors, tacrolimus and ciclosporin, are two useful immunosuppressive drugs for the treatment of myasthenia gravis (MG), for patients who have low responses to glucocorticoids. We have studied the suppressive potencies of tacrolimus and ciclosporin on concanavalin A-induced blastogenesis of peripheral-blood mononuclear cells (PBMCs) obtained from 38 MG patients and 26 healthy volunteers. Differences in the IC50 values of the two calcineurin inhibitors between the patients and the healthy subjects were evaluated. The median (range) IC50 values for tacrolimus and ciclosporin on the blastogenesis of PBMCs of MG patients were 0.06 (0.001–100) and 0.41 (0.09–83.0) ng mL−1, respectively. In contrast, the median (range) IC50 values of tacrolimus and ciclosporin on healthy PBMCs were 0.16 (0.001–0.33) and 5.59 (1.4–31.3), respectively, and thus ciclosporin potencies against PBMCs of MG patients were significantly higher than those against PBMCs of healthy subjects (P < 0.0001). The differences in tacrolimus IC50 values between the patients and healthy subjects were not significant. There was a correlation between ciclosporin IC50 values against the blastogenesis of PBMCs of MG patients and the duration of the disease (r = 0.35, P = 0.049). A significant correlation between the IC50 values of ciclosporin and those of prednisolone against the blastogenesis of PBMCs of MG patients was also observed (r = 0.56, P = 0.003). Furthermore, the ciclosporin IC50 values significantly correlated with the periods of glucocorticoid administration for MG treatment (r = 0.42, P = 0.038). Such correlations were not observed with the tacrolimus IC50 values. These results suggested that glucocorticoid administration had an influence on PBMC response to the suppressive efficacy of ciclosporin in MG.

Comparative Study of the Cellular Pharmacodynamics of Calcineurin Inhibitors between Patients with Chronic Renal Failure Awaiting Renal Transplantation and Cirrhosis Patients Awaiting Liver Transplantation

The in vitro response of peripheral blood mononuclear cells (PBMCs) to the suppressive effects of calcineurin inhibitors is known to correlate with the clinical efficacy of drugs used in renal transplantations. The present study was conducted to examine the differences of PBMC responses to calcineurin inhibitors between chronic renal failure (CRF) patients awaiting renal transplantation and cirrhosis patients awaiting liver transplantation. The study included 99 CRF patients awaiting renal transplantation and 27 cirrhosis patients awaiting liver transplantation. Twenty milliliters of venous blood was taken 1-7 days before transplantation. The in vitro drug concentrations giving 50% inhibition of PBMC blastogenesis stimulated with concanavalin A (IC(50)s) were calculated. The suppressive effects of tacrolimus against PBMC blastogenesis were more than 10-100 times stronger than those of cyclosporine. The median IC(50) value for cyclosporine against the CRF PBMCs was not significantly different from the median IC(50) value against the cirrhosis PBMCs. In contrast, tacrolimus sensitivity in cirrhosis PBMCs is approximately seven times higher than that in CRF PBMCs. The median IC(50) value for tacrolimus against cirrhosis PBMCs was significantly lower and therefore the effect was stronger in comparison to the CRF PBMCs (p < 0.001). These data suggest that the PBMCs of cirrhosis patients, in comparison to those of CRF patients, are highly sensitive to the suppressive effect of tacrolimus. However, PBMC sensitivity to cyclosporine was not significantly different between the CRF and cirrhosis patients. These observations raise the possibility that treatment with tacrolimus, rather than cyclosporine, may therefore be a better choice to reduce the risks of allograft rejection in liver transplantation.

Clinical Significance of the Cellular Pharmacodynamics of Tacrolimus in Living-Donor Liver Transplantation

Successful immunosuppressive therapy is critical for liver transplantation; however, a considerable number of patients experience fatal rejection or alternatively exhibit serious infection resulting from excessive immunosuppression. The in vitro tacrolimus response of peripheral blood mononuclear cells (PBMCs) before transplantation was compared to the clinical outcome up to 4 weeks after operation in 28 living-donor liver transplant recipients treated with tacrolimus. The tacrolimus IC(50) values against concanavalin A-induced PBMC blastogenesis in vitro were calculated. These recipients were classified into two groups with the mean tacrolimus IC(50) (0.18 ng/ml) as the cutoff point, after which the clinical outcome between the patient groups was compared. The allograft rejection incidence in the low-sensitivity group (IC(50) < 0.18 ng/ml; n = 16) was 6/12 (50.0%), which was significantly higher than the incidence of 2/16 (12.5%) in the high-sensitivity group (IC(50) > 0.18 ng/ml; n = 12) (p = 0.0297). In contrast, the infection incidence in the high-sensitivity group was 6/16 (37.5%), which was significantly higher than that of the low-sensitivity group (1/12; 8.3%) (p = 0.0401). These data suggest that patients exhibiting a low PBMC sensitivity to tacrolimus have a risk of rejection, whereas highly sensitive patients have a risk of infection in living-donor liver transplantations under tacrolimus therapy.

Suppressive potencies of calcineurin inhibitors against the mitogen-induced blastogenesis of peripheral-blood mononuclear cells of myasthenia gravis patients

The calcineurin inhibitors, tacrolimus and ciclosporin, are two useful immunosuppressive drugs for the treatment of myasthenia gravis (MG), for patients who have low responses to glucocorticoids. We have studied the suppressive potencies of tacrolimus and ciclosporin on concanavalin A-induced blastogenesis of peripheral-blood mononuclear cells (PBMCs) obtained from 38 MG patients and 26 healthy volunteers. Differences in the IC50 values of the two calcineurin inhibitors between the patients and the healthy subjects were evaluated. The median (range) IC50 values for tacrolimus and ciclosporin on the blastogenesis of PBMCs of MG patients were 0.06 (0.001-100) and 0.41 (0.09-83.0) ng mL(-1), respectively. In contrast, the median (range) IC50 values of tacrolimus and ciclosporin on healthy PBMCs were 0.16 (0.001-0.33) and 5.59 (1.4-31.3), respectively, and thus ciclosporin potencies against PBMCs of MG patients were significantly higher than those against PBMCs of healthy subjects (P < 0.0001). The differences in tacrolimus IC50 values between the patients and healthy subjects were not significant. There was a correlation between ciclosporin IC50 values against the blastogenesis of PBMCs of MG patients and the duration of the disease (r = 0.35, P = 0.049). A significant correlation between the IC50 values of ciclosporin and those of prednisolone against the blastogenesis of PBMCs of MG patients was also observed (r = 0.56, P = 0.003). Furthermore, the ciclosporin IC50 values significantly correlated with the periods of glucocorticoid administration for MG treatment (r = 0.42, P = 0.038). Such correlations were not observed with the tacrolimus IC50 values. These results suggested that glucocorticoid administration had an influence on PBMC response to the suppressive efficacy of ciclosporin in MG.

Influence of Bacterial Superantigen TSST-1 Against the Anti-Proliferative Efficacy of Immunosuppressive Drugs and Interleukin 2 Production in Peripheral Blood Mononuclear Cells of Hemodialysis Patients and Healthy Subjects

We investigated the influence of bacterial superantigen on the efficacies of immunosuppressive drugs on the blastogenesis of peripheral-blood mononuclear cells of 27 hemodialysis patients awaiting renal transplantation. The IC50 values for prednisolone, methylprednisolone, cyclosporine, and tacrolimus evaluated in the superantigen-stimulated cells were significantly higher than those evaluated in concanavalin A-stimulated cells (p = 0.0002–0.018). Interleukin-2 amounts produced from superantigen-stimulated cells were significantly larger than those from concanavalin A-stimulated cells (p = 0.0363). These results suggest that superantigen attenuates the suppressive efficacies of glucocorticoids and calcineurin inhibitors by stimulating lymphocytes of hemodialysis patients awaiting transplantation to overproduce interleukin-2.

Bacterial superantigen TSST-1 attenuates suppressive efficacy of glucocorticoids and calcineurin inhibitors against blastogenesis of peripheral blood mononuclear cells from patients with chronic renal failure on hemodialysis treatment

Backgrounds Many cases of patients with chronic renal failure (CRF) on hemodialysis are known to be infected with Staphylococcus aureus ( S. aureus) from the sites of blood vessel puncture for hemodialysis and the custody of the vascular access catheter. S. aureus produces superantigens, such as toxic shock syndrome toxin-1 (TSST-1), which may influence the sensitivity of peripheral-blood mononuclear cells (PBMCs) to immunosuppressive drugs after they are received postrenal transplantation. Methods We examined the drug-sensitivities of PBMCs stimulated with TSST-1 in 18 CRF patients on hemodialysis. PBMCs were isolated from venous blood before hemodialysis, and were cultured in the presence of concanavalin A (ConA) or TSST-1 and serial concentrations of the drugs. In vitro drug concentrations giving 50% inhibition (IC 50) of PBMC blastogenesis were calculated. INF-γ and IL-4 in supernatants of cultured PBMCs were measured with ELISA. Results The median (range) IC 50 values (ng/ml) for four drugs; tacrolimus, cyclosporine, methylprednisolone, and prednisolone, evaluated in ConA-stimulated PBMCs of CRF patients were 0.04 ng/ml (0.03–0.21), 3.0 (0.1–15.1), 3.0 (1–104), and 16.2 (5.9–35.4), respectively. The values for the four drugs evaluated in TSST-1-stimulated PBMCs were 0.22 (0.08–0.36), 18.9 (5.1–38.2), 328.3 (1.9–1000), and 150.9 (94.7–880), respectively, which were significantly higher than those evaluated in the ConA-stimulated PBMCs ( p = 0.003–0.023). Amounts of INF-γ and IL-4 produced from cells were not significantly different between the ConA-or TSST-1-stimulated PBMCs in the presence or absence of immunosuppressive drugs. Conclusion These observations raise the possibility that TSST-1 induced by S. aureus infection attenuates the clinical efficacy of glucocorticoids and calcineurin inhibitors in CRF patients after renal transplantation. Furthermore, INF-γ and IL-4 related pathways appear not to play major roles in the TSST-1-induced attenuation of the drug sensitivities.

Immunosuppressive efficacy of mycophenolate mofetil when compared with azathioprine and mizoribine against peripheral lymphocytes from renal transplant recipients

Mycophenolate mofetil is currently used instead of azathioprine in clinical transplantation. However, comparative studies for the immunosuppressive potency of anti-metabolites used for organ transplantation have not been well documented. We compared the pharmacological efficacy of mycophenolic acid (MPA), 6-meraputopurine (6-MP), and mizoribine (MZ) for inhibiting purine synthesis of peripheral blood mononuclear cells (PBMCs) in vitro by a mitogen assay procedure. PBMCs were obtained from 18 renal transplant recipients before operation and 18 healthy subjects. The inhibitory efficacy of 6-MP against concanavalin A-induced PBMC blastogenesis exhibited large variations between subjects in both recipients and healthy subjects. In contrast, the pharmacological efficacy of MPA on PBMC blastogenesis showed the smallest inter-individual variation of all the purine synthesis inhibitors examined. Furthermore, the effects of MPA were almost similar in the recipients and healthy subjects. The pharmacological efficacy of MZ against PBMC blastogenesis was weaker than that of the other two agents and the inter-individual variation of MZ IC50 against PBMCs of the patients was larger than that of MZ IC50 against PBMCs of healthy subjects. Reproducible immunosuppressive efficacy of MPA compared with other purinesynthesis inhibitors could be expected from the viewpoint of MPA pharmacodynamics against PBMCs in renal transplantation.

EVALUATION OF P-GLYCOPROTEIN EXPRESSION AND FUNCTION IN PERIPHERAL-LYMPHOCYTES OF RENAL TRANSPLANT RECIPIENTS: RELATIONSHIP WITH LYMPHOCYTE-SENSITIVITY TO IMMUNOSUPPRESSIVE DRUGS AND CLINICAL STATUS.

P719 Aims: P-glycoprotein (P-gp) is reported to mediate the efflux of several lipophilic drugs from mammalian cells. Overexpression of P-gp in immune cells may result in the insufficient efficacy of immunosuppressive drugs in renal transplantation patients. With this in mind, we evaluated P-gp expression and function in peripheral-blood mononuclear cells (PBMCs) to examine their influence on PBMC-sensitivity to immunosuppressive drugs and the clinical status of renal transplant recipients. Methods: Seventeen renal transplant recipients, nine patients with chronic renal failure, and 16 healthy subjects were included in the study. The basic characteristics of these subject groups did not differ significantly. Out of the 17 transplant recipients, 14 had received cyclosporine-based immunosuppressive therapy, while two patients received tacrolimus and one a steroid without calcineurin inhibitors. P-gp expressed in PBMCs was stained with FITC-labeled anti-P-gp monoclonal antibodies and subsequently analyzed with flow cytometry. P-gp function was evaluated with incorporation and efflux of rhodamine 123 (R123) in the presence or absence of cyclosporine, followed by flow cytometry analysis. PBMC-sensitivity to the suppressive effects of prednisolone, methylprednisolone, cyclosporine or tacrolimus was evaluated by measuring the IC50s (ng/ml) of these agents against concanavalin A-induced blastogenesis of PBMCs in vitro. Results: The incidence of transplant recipients with PBMCs exhibiting high-rates of P-gp expression was significantly higher than that of the healthy subjects (p=0.0035). However, percentages of P-gp expressing PBMCs and P-gp function evaluated by R123-efflux ability of the cells did not correlate significantly in either of the subject groups. The IC50s of the immunosuppressive drugs did not correlate with the percentage of cells expressing P-gp or P-gp function in the PBMCs of the transplant recipients. In addition, we found no statistically significant correlation between these P-gp parameters and other clinical characteristics of the recipients such as the incidence of rejection episodes or adverse effects of the immunosuppressive drugs administered. In contrast, the amount of R123 incorporated and retained in the PBMCs significantly correlated with either serum creatinine or blood urea nitrogen (BUN) concentrations in transplant recipients (p=0.021 and p=0.0014, respectively). Conclusions: We conclude that P-gp expression and its function in PBMCs had little influence on the cellular and clinical pharmacodynamics of immunosuppressive drugs in the renal transplant recipients. Increases in concentrations of serum creatinine, BUN, and/or possibly other uremic toxin(s) due to the impairment of renal graft function results from chronic allograft rejection or cyclosporine side effects may have suppressed the P-gp function in the PBMCs of these recipients.

The effects of extracorporeal whole body hyperthermia on the functional and phenotypic features of canine peripheral blood mononuclear cells (PBMC).

In this study the effect of transient 42.3 degrees C whole body hyperthermia (WBH) on the distribution of PBMC phenotypes and in vitro blastogenic responsiveness was determined in dogs. Hyperthermia (n = 6) was induced by heating venous blood during extracorporeal circulation (venous perfusion WBH); perfused non-heated dogs (n = 4) were used as controls. Both euthermic and hyperthermic perfusion produced transient lymphopenia which normalized in controls after perfusion but persisted in hyperthermic animals throughout the 8-day post-perfusion observation interval. The transient lymphopenia in control dogs was non-selective. In contrast, WBH-associated lymphopenia was selective, in that CD5+ T lymphocytes were more sensitive to hyperthermia than sIg+ B cells and, within the T cell compartment, suppressor (CD8+) cells were more sensitive to hyperthermic stress than helper (CD4+) lymphocytes. Functional analyses showed that WBH caused persistent suppression of PBMC blastogenesis in response to T cell phytomitogens. Increased plasma cortisol levels were correlated to peak lymphopenia and hyporesponsiveness to phytomitogens. Despite these alterations, high grade WBH was well tolerated and there was no evidence of opportunistic infection.

Comparative study of lymphocyte-suppressive potency between prednisolone and methylprednisolone in rheumatoid arthritis

We compared lymphocyte-suppressive potencies of prednisolone and methylprednisolone in rheumatoid arthritis (RA). IC50s of the glucocorticoids (GCs) on concanavalin A-induced blastogenesis of peripheral-blood mononuclear cells (PBMCs) from 44 RA patients and 30 healthy subjects were estimated in vitro, and differences in the IC50s of the two GCs were evaluated. The mean (±SD) IC50s for prednisolone and methylprednisolone on PBMC-blastogenesis of RA were 17.2±17.1 and 12.6±18.4 ng/ml, respectively, and no significant differences were observed between prednisolone-IC50 and methylprednisolone-IC50. In contrast, the mean IC50s of prednisolone and methylprednisolone on healthy PBMCs were 19.4±22.4 and 3.7±3.9 ng/ml, respectively, and thus methylprednisolone potency was significantly higher than prednisolone potency (p<0.01). Methylprednisolone potency against PBMCs in RA patients exhibiting a high level of rheumatoid factor (RF) (>20 IU/ml) and the rheumatoid arthritis particle-agglutination value (RAPA) (>80) was significantly higher than that of patients exhibiting a lower level of RF or RAPA (p<0.05). In prednisolone-IC50, however, such differences between the two patient-subgroups were not observed. Unlike reported cases of renal transplantation and healthy subjects, there was no difference in the lymphocyte-suppressive potencies for both prednisolone and methylprednisolone on RA-PBMCs. However, PBMCs from RA patients exhibiting high levels of RF or RAPA are more sensitive to methylprednisolone rather than prednisolone.

Effects of fighting after grouping on plasma cortisol concentration and lymphocyte blastogenesis of peripheral blood mononuclear cells induced by mitogens in piglets.

One litter (Group A) of three unacquainted groups of littermates (4 piglets/litter), 64.0 +/- 0.8 days old, was moved to the pen of another litter (Group B) and they were housed together for 19 days after grouping (phase 1). The pigs in Group B violently attacked all the pigs in Group A for 9 hr after grouping. The remaining group was not grouped and used as controls. The plasma cortisol concentrations 1 hr after grouping were significantly higher than those 1 hr before and 24 hr after grouping, and the suppression of lymphocyte blastogenesis of peripheral blood mononuclear cells (PBMC) induced by mitogens was observed on 3, 8 and 19 days after grouping. After phase 1 ended, the pigs in Group A were returned to their own pen for 7 days, and then they were regrouped with the pigs in Group B and reared together for a further 14 days. Neither agonistic behavior nor change of plasma cortisol after regrouping was seen. Though the lymphocyte blastogenesis of PBMC induced by the mitogens on day 0 after regrouping was significantly lower in the pigs of Groups A and B compared to those in control pigs, a significant difference in lymphocyte blastogenesis among three groups was not seen on 7 and 14 days after regrouping. These findings indicate that fighting after grouping unacquainted litters increases plasma cortisol, and suppresses lymphocyte blastogenesis for 26 days after grouping.

Potent growth inhibitory activity of a novel Ornithogalum cholestane glycoside on human cells: Induction of apoptosis in promyelocytic leukemia HL-60 cells

Growth inhibitory activities of a novel 22-homo-23-norcholestane glycoside found in bulbs of Ornithogalum saundersiae were examined in vitro using human promyelocytic leukemia HL-60 cells, human T-lymphocytic leukemia MOLT-4 cells, and mitogen-stimulated human peripheral-blood mononuclear cells (PBMC). The growth of HL-60 cells and MOLT-4 cells was strongly suppressed in the presence of the glycoside; the IC 50s of which were 21.0 and 18.0 nM, respectively. Suppressive effect of the glycoside on HL-60 cell growth appears to be mediated partially through induction of apoptosis which was demonstrated by the presence of DNA fragmentation of the leukemic cells. Flow cytometric analysis of glycosidetreated HL-60 cells also demonstrated apoptotic cells with low DNA content and showed a decrease of G0 G1 cells and a concomitant increase of S and/or G2 M cells. The growth inhibiting effect of the glycoside on HL-60 cells was promoted by calcium and was inhibited in the presence of zinc, which support involvement of endonuclease activation in the glycoside-induced apoptosis. The glycoside also inhibited mitogenstimulated blastogenesis of PBMC, the IC 50 of which was 6.2 nM. These results provided the first evidence ever for the potent growth inhibitory activity of Ornithogalum glycoside on human leukemia cell lines and PBMC.

Citrus flavone tangeretin inhibits leukaemic HL-60 cell growth partially through induction of apoptosis with less cytotoxicity on normal lymphocytes

Certain anti-cancer agents are known to induce apoptosis in human tumour cells. However, these agents are intrinsically cytotoxic against cells of normal tissue origin, including myelocytes and immunocytes. Here we show that a naturally occurring flavone of citrus origin, tangeretin (5,6,7,8,4'-pentamethoxyflavone), induces apoptosis in human promyelocytic leukaemia HL-60 cells, whereas the flavone showed no cytotoxicity against human peripheral blood mononuclear cells (PBMCs). The growth of HL-60 cells in vitro assessed by [3H]thymidine incorporation or tetrazolium crystal formation was strongly suppressed in the presence of tangeretin; the IC50 values range between 0.062 and 0.173 microM. Apoptosis of HL-60 cells, assessed by cell morphology and DNA fragmentation, was demonstrated in the presence of > 2.7 microM tangeretin. Flow cytometric analysis of tangeretin-treated HL-60 cells also demonstrated apoptotic cells with low DNA content and showed a decrease of G1 cells and a concomitant increase of S and/or G2/M cells. Apoptosis was evident after 24 h of incubation with tangeretin, and the tangeretin effect as assessed by DNA fragmentation or growth inhibition was significantly attenuated in the presence of Zn2+, which is known to inhibit Ca(2+)-dependent endonuclease activity. Ca2+ and Mg2+, in contrast, promoted the effect of tangeretin. Cycloheximide significantly decreased the tangeretin effect on HL-60 cell growth, suggesting that protein synthesis is required for flavonoid-induced apoptosis. Tangeretin showed no cytotoxicity against either HL-60 cells or mitogen-activated PBMCs even at high concentration (27 microM) as determined by a dye exclusion test. Moreover, the flavonoid was less effective on growth of human T-lymphocytic leukaemia MOLT-4 cells or on blastogenesis of PBMCs. These results suggest that tangeretin inhibits growth of HL-60 cells in vitro, partially through induction of apoptosis, without causing serious side-effects on immune cells.

In vitro influence of Mycoplasma penetrans on activation of peripheral T lymphocytes from healthy donors or human immunodeficiency virus-infected individuals.

Mycoplasma penetrans is a mycoplasma species newly isolated from the urine of human immunodeficiency virus (HIV)-infected individuals and presents the only case in which an association has been found between antibodies against a mycoplasma and HIV infection. To further explore the effects of M. penetrans on the immune system, we studied the influence of this mycoplasma on peripheral blood mononuclear cells (PBMCs) from healthy donors and HIV-infected individuals. M. penetrans induced, in addition to blastogenesis of PBMCs, a significant proliferative response associated with the expression of some activation markers such as CD69, HLA-DR, and CD25. This M. penetrans-dependent lymphocyte activation was observed not only in healthy donors but also in HIV-infected persons at different stages of the disease. In addition, our study revealed that both CD4+ and CD8+ T lymphocytes were responsive to M. penetrans. Interestingly, the mitogenic activity of M. penetrans was associated with mycoplasma cells but not with the supernatants of mycoplasma culture. The potent stimulating activity of M. penetrans on T lymphocytes from HIV-infected individuals is of particular interest in view of the supposed contribution of immune activation to HIV replication and disease progression.

Blastogenic responses and production of TCGF by mononuclear cells isolated from the bovine endometrium

Mononuclear cells (MNCs) were isolated from the endometrium of cattle by enzymatic digestion followed by centrifugation on a density gradient. Of the cells isolated, 32±3.2% rosetted AET-treated sheep red blood cells, 9±0.4% possessed surface membrane immunoglobulin, and 15±6.1% were esterase positive. The cells possessed the ability to proliferate in the presence of T cell mitogens and produced T cell growth factor (TCGF) after in vitro stimulation with Concanavalin A. Endometrial MNCs did not appear to suppress the blastogenesis of peripheral blood MNCs.

Increased interleukin-1 production and monocyte suppressor cell activity associated with human tuberculosis.

Interleukin-1 (IL-1) production by blood monocytes and blastogenesis produced by tuberculin purified protein derivative (PPD) in blood T lymphocytes were examined in patients with pulmonary tuberculosis. Monocytes were isolated from blood mononuclear cells by plastic adherence, and IL-1 activity was determined in the mouse thymocyte proliferation assay. Monocytes from patients with tuberculosis produced significantly higher activities of IL-1 than did those from healthy tuberculin reactors when stimulated with lipopolysaccharide (LPS) (patients, 56.1 +/- 20.0 U/ml; healthy control subjects, 7.3 +/- 1.7 U/ml; p less than 0.05) or PPD (patients, 28.1 +/- 7.2 U/ml; healthy control subjects, 9.5 +/- 2.9 U/ml; p less than 0.05). In contrast, PPD-induced blastogenic responses in peripheral blood mononuclear cells (PBMC) from the patients were lower than those from healthy subjects (patients, 4,506 +/- 1,145 cpm; healthy control subjects, 14,655 +/- 2,240 cpm; p less than 0.005), and IL-1 production by monocytes showed a positive correlation with monocyte suppressor activity for PPD-induced blastogenesis. Moreover, exogenous IL-1 was capable of suppressing antigen-induced blastogenesis of PBMC from healthy subjects. These data suggest that monocytes from patients with pulmonary tuberculosis are activated to produce or secrete increased levels of IL-1 and that IL-1 may be a mediator of suppressor cell function.