Immunosuppressant Activity of the Ansamycins

Kasik, John E.; Monick, Martha M.; Thompson, John S.

doi:10.1128/aac.9.3.470

Cited by 10 publications

(8 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Treatment of mice with the five rifamycins resulted in a significant suppression of DTH as measured by their footpad reactions to partially purified protein derivative in several instances. This suppression was similar to that previously noted with other ansamycins (6).…”

Section: Resultssupporting

confidence: 77%

“…Rifamycin formo-S was active when the mice received a dose of 100 mg/ kg per day. This was a dose of antibiotic which had been shown to be ineffective with rifampin used under identical conditions in previous experiments (6). Thus, it can be said that although the in vivo differences in activity were not great, rifamycin formo-S appeared to be the most active substance studied in vivo, as it was in vitro, and that rifamide was the least active substance studied in both systems.…”

Section: Resultsmentioning

confidence: 90%

“…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: 77%

“…The methods used to determine the in vitro susceptibility of M. tuberculosis to the five rifamycins were identical to those previously published (6). Growth of the organisms was measured 7 days after adding the antibiotics.…”

mentioning

confidence: 99%

“…In vivo studies. Assay of the in vivo effect of the rifamycins on delayed-type hypersensitivity (DTH) was performed in mice by methods described in detail elsewhere (6). In brief, the animals were immunized with the R1R, strain of M. tuberculosis, and the resulting immunity was tested by injecting 250 units of partially purified protein derivative (Connaught Laboratories, Willowdale, Ontario, Canada) into the hind footpad.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Comparison of antibacterial and antiimmune effects of certain rifamycins

Kasik¹,

Monick²

1981

Antimicrob Agents Chemother

View full text Add to dashboard Cite

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...

show abstract

Section: Resultssupporting

confidence: 77%

Section: Resultsmentioning

confidence: 90%

mentioning

confidence: 77%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations