Protection from O,O,S-trimethyl phosphorothioate-induced immune suppression.
Acute administration of nontoxic doses of an impurity in technical malathion, O,O,S-trimethyl phosphorothioate (OOS-TMP), was able to block the in vitro generation of cytotoxic T lymphocytes (CTL) to alloantigen and antibody-secreting cells (Ab) to sheep red blood cells (SRBC). The effects of an antagonist of the delayed toxicity and lung damage of OOS-TMP, O,O,O-trimethyl phosphorothionate (OOO-TMP), and pretreatment of tolerance-inducing doses of OOS-TMP on OOS-TMP-induced immune suppression were examined. Treatment groups included (A) acute administration of OOO-TMP, (B) coadministration of OOO-TMP with OOS-TMP (at concentrations which have been shown previously to block lung toxicity). (C) repeated (4 x on consecutive days) administration of OOS-TMP (which was shown previously to block a lung toxicity which occurs following a challenge with OOS-TMP) and (D) repeated administration of OOS-TMP followed by a challenge dose of OOS-TMP 24 h before death. There was no change in lymphoid organ size following any of these treatments. However, splenocytes from animals that were exposed to treatment regimes A, B and D had significantly elevated proliferative responses to mitogens concanavalin A (ConA) and lipopolysaccharide (LPS). The ability of splenocytes to generate an Ab response to SRBC was significantly elevated following treatment regime A and at the lower dose in treatment regime D. All other treatment protocols did not alter this immune parameter. There was no difference in the ability of splenocytes to generate a CTL response following these treatment regimes. In conclusion, the degree of protection from immune suppression by these treatments which have been shown to protect against lung toxicity varied with the sensitivity of the immune parameters to suppression by acute administration of OOS-TMP.
Division of Biomedical Sciences, University of California, Riverside 92521-0121.
K E
KE
Rodgers
D L
DL
Haviland
C F
CF
Ware
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D005260:Female; D007166:Immunosuppressive Agents / Q000633:toxicity*; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D063086:Organothiophosphates / Q000633:toxicity
D007166:Immunosuppressive Agents; D063086:Organothiophosphates; C023890:O,O,O-trimethyl phosphorothioate; C019123:O,O,S-trimethyl phosphorothioate