Immunosuppressive Agents

Evidence for the synthesis and release of strongly immunosuppressive, noncytotoxic substances by Streptococcus intermedius.

“…As for other substances extracted from or produced by bacteria (11)(12)(13)(14)(15)(16)(17)(18) which are not toxins, it was found that CEP-Si was not cytotoxic, as shown by (a) the viability and proliferative ability of cells incubated with large doses and then washed, (b) its lack of inhibition of normal migration of PMN effects of some bacterial substances -e.g., lipoteichoic acid (15)-may represent competition between these substances and antigens as a result of blocking of the relevant receptors (11). These studies clearly exclude this possibility for the products secreted by S. intermedius, as they can strongly suppress the immune response to a variety of antigens, as well as cell proliferation in response to several mitogens.…”

“…This hypothesis would also explain why the suppressor effects of CEP-Si are greater in MLC-than PPD-stimulated cultures and greater in the latter than in PHA-stimulated cultures. These observations, which suggest that CEP-Si can induce the generation of suppressor cells, indicate a lack of similarity between CEP-Si and immunosuppressive enzymes secreted by other bacteria (16)(17)(18). Indeed, the enzymatic suppressor effect is assumed to be a result of the destruction of essential cellular nutrients, such as amino acids (11), and therefore their effects are more likely a result of inhibition of helper and effector cells.…”

“…It is also conceivable, however, as noted by Schwab (11), that the infecting microorganisms could produce substances (not necessarily toxins) directly able to suppress the host's immune response in order to survive in an adverse environment. Previous studies have shown suppressive effects ofnoncytotoxic cellular extracts from group A streptococci and of streptococcal lipoteichoic acid on immune responses of mice in vivo (12)(13)(14)(15); however, in vitro suppression by these substances either was not studied or when studied was not observed (14), although noncytotoxic immunosuppression in vitro and in vivo by enzymes secreted by bacteria, such as ribonuclease (16), L-glutamine (17), and asparaginase (18), has been reported.…”

Inhibitory and Stimulatory Effects of Dianhydrogalactitol, an Alkylating Cytostatic Agent on the Humoral Immune Response

“…The drug proved to be effective and well tolerated also in humans. DAG had a suppressive effect on the immune system inhibiting the in vitro cytostatic activity of lym phocytes [14] and the humoral immune responsiveness of rats [5], Alterations in the immunomodulating ef fect depending on dose or schedule of treatment were described with numerous cytostatic agents [3,8,10]. This work was done to clarify to what extent the dose and time of DAG treatment would influence the hu moral immune response to sheep red blood cell (SRBC) antigen.…”

Enhancement of Immune Responses in Tumor-Bearing Mice after Administration of <i>cis</i>-Diamino-dichloro-platinum (II)

“…The effects of anticancer agents on the immune system are complex and generally cause a depression of immune response [9], However, when the drug is administered before the antigenic challenge it may be possible to obtain an enhancement of the response against the antigen [3,17], For the immune system functioning, both amplifi cation and suppression of the immune response are critical, and these functions depend on different cell populations. This response may be modulated by se lective elimination of any of the cell populations in volved.…”