Effect of Rifampin on the Immune Response in Guinea Pigs

Rifampin has been shown to impair both humoral and cell-mediated immune responses in animal models. In order to detect a similar effect in man, 11 patients with active tuberculosis were evaluated before, 2 weeks after, and 12 to 16 weeks after initiating rifampin. Several parameters were serially measured including blood lymphocytes, intradermal response to intermediate strength tuberculin (PPD), and in vitro proliferative responses to phytohemagglutinin (PHA), a nonspecific mitogen, and to the specific antigens, PPD and influenza A. No changes in lymphocyte counts were noted. No changes in response were noted 2 weeks after beginning treatment with rifampin. However, compared with initial and 2-week responses, the PHA response was reduced by 47%, the PPD by 68%, and the influenza by 75%, and 6 of 11 patients showed no induration after tuberculin skin testing at the 12-to 16-week point. These results indicate that in doses employed for the treatment of tuberculosis, rifampin has an immunosuppressive effect in man that develops gradually.

Section: Ruben Winkelstein and Fotiadissupporting

confidence: 81%

Immunological Responsiveness of Tuberculosis Patients Receiving Rifampin

Ruben

Winkelstein

Fotiadis

1974

“…The dose of rifampin required to suppress the footpad reaction to PPD in this animal species was large when compared with the dose required to produce a similar effect in guinea pigs (2). In guinea pigs 20 mg of oral rifampin per kg partially suppressed the intradermal reaction to PPD in 14 days, but in mice 200 mg of parenteral rifampin per kg per day was required to produce significant suppression of that reaction ( Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…the antibody response to sheep erythrocytes (2). Thus, the antibiotic can inhibit both cell-mediated immunity (CMI) and antibody-mediated immunity.…”

mentioning

confidence: 99%

Immunosuppressant Activity of the Ansamycins

Kasik

Monick

Thompson

1976

The immunosuppressive effect of four analogues of rifampin and two streptovaracins on cell-mediated immunity has been determined. Tuberculin hypersensitivity in the footpads of immunized mice was inhibited by three ofthe rifampin analogues and by both streptovaracins. The observed in vivo immunosuppressive activity of the compounds tested was not correlated with their in vitro activity against mycobacterial growth but was associated with their toxicity in mice. These data indicate that some of the analogues of rifampin and the streptovaracins can significantly suppress cell-mediated immunity and suggest that other ansamycins may have significant immunosuppressant activity.

“…Antibacterial activity in cultures and the activities of the rifamycins inhibiting deoxyribonucleic acid-dependent ribonucleic acid polymerase appeared to correlate well. However, when these two types of activity, antiimmune and antibacterial, were compared, correlation was poor on occasion and indicated that the antiimmune activities and antibacterial activities of the rifamycins are probably not related.It has been reported previously (6) that some members of the ansamycin class of antibiotics, including certain rifamycins and streptovaricins, share the well-recognized immunosuppressive properties of rifampin (3,4,8,11). It was noted in that report that when the in vitro antibacterial activity of these substances was compared with their in vivo immunosuppressive activity, correlation was poor, suggesting that the two activities are unrelated.…”

mentioning

confidence: 78%

“…It has been reported previously (6) that some members of the ansamycin class of antibiotics, including certain rifamycins and streptovaricins, share the well-recognized immunosuppressive properties of rifampin (3,4,8,11). It was noted in that report that when the in vitro antibacterial activity of these substances was compared with their in vivo immunosuppressive activity, correlation was poor, suggesting that the two activities are unrelated.…”

mentioning

confidence: 83%

Comparison of antibacterial and antiimmune effects of certain rifamycins

Kasik¹,

Monick²

1981

Comparison of the in vivo and in vitro immunosuppressive activities of the five rifamycins with their in vitro antibacterial and anti-ribonucleic acid polymerase activities indicated that correlation was poor. Examination of their activities on mitogen-induced blastogenesis in human peripheral blood leukocytes and inhibition of delayed-type hypersensitivity to partially purified protein derivative in immunized mice demonstrated that correlation was usually good. Antibacterial activity in cultures and the activities of the rifamycins inhibiting deoxyribonucleic acid-dependent ribonucleic acid polymerase appeared to correlate well. However, when these two types of activity, antiimmune and antibacterial, were compared, correlation was poor on occasion and indicated that the antiimmune activities and antibacterial activities of the rifamycins are probably not related.It has been reported previously (6) that some members of the ansamycin class of antibiotics, including certain rifamycins and streptovaricins, share the well-recognized immunosuppressive properties of rifampin (3,4,8,11). It was noted in that report that when the in vitro antibacterial activity of these substances was compared with their in vivo immunosuppressive activity, correlation was poor, suggesting that the two activities are unrelated.The following is a report of studies of the immunosuppressant activity of five rifamycins, chosen because they had large differences in antibacterial activity. Comparison of the antibacterial and immunosuppressant activities of these compounds demonstrated that their in vitro antimicrobial activity was often unrelated to their in vivo and in vitro immunosuppressive effects.MATERIALS AND METHODS Rifamycins used. The following rifamycins were kindly supplied by Gruppo Lepetit, Milano, Italy (the minimal inhibitory concentrations required for Mycobacterium tuberculosis, as determined in Lepetit's laboratory, are within parentheses): rifampin (0.5 ug/ ml), rifamycin SV (0.05 Ag/ml), rifamide (0.2 ytg/ml), 8 methyl-rifamycin (5 tLg/ml), and rifamycin formo-S (5 jg/ml). (See Results.) Rifamycins were prepared for use by dissolving them in a minimal volume of a 1:10 mixture of dimethyl sulfoxide (Me2SO) (Mallinckrodt, St. Louis, Mo.) and fetal calf serum (Grand Island Biological Co., Grand Island, N.Y.). This solution was further diluted with a volume of physiological saline sufficient to provide the desired concentration of drug. Solutions used for control studies contained a concentration of Me2SO and fetal calf serum in saline equal to the drugcontaining solutions.Inhibition of in vitro blastogenesis. The effects of the rifamycins studied on mitogen-induced blastogenesis were assayed by using human peripheral blood leukocytes. Blood was drawn from healthy donors into heparinized tubes, and the leukocytes were isolated and cultured by the method of Thompson et al. (14) and by the microculture technique with 5 x 104 cells in 0.2 ml of Eagle medium supplemented with pooled human AB plasma, penicillin, streptomycin, an...