Suppression of humoral and cell-mediated immune responses by carbon tetrachloride

The effects of carbon tetrachloride (CCl4), following 7 consecutive days of exposure ip at 500, 1000, and 1500 mg/kg, were determined on murine humoral and cell-mediated immune responses, body and organ weights, spleen cell blastogenesis following mitogenic stimulation, and clinical serum parameters for liver injury. In vivo sensitization of CCl4-treated B6C3F1 mice resulted in a dose-dependent suppression of the T-dependent antibody response to sheep red blood cells (sRBC) at all doses--36, 48, and 53%, respectively. The T-independent in vivo antibody response to DNP-Ficoll was suppressed only at 1500 mg/kg, and only by approximately 16%. This dosing regimen also resulted in a significant decrease in thymus weights; however, there were no significant effects on liver, kidney, lung, or body weights. The serum chemistry profile indicated a dose-dependent increase in serum glutamic-pyruvic transaminase (SGPT) levels (34-, 47-, and 55-fold) and a non-dose-dependent increase in serum bilirubin and total protein. Serum glucose and albumin levels were unaffected. Splenocytes from mice treated with 1500 mg/kg and sensitized in vitro with antigen demonstrated a comparably suppressed antibody response to the antigens sRBC and DNP-Ficoll as observed in vivo--66 and 28% respectively. This dose of CCl4 had no effect on the in vitro antibody response to the polyclonal antigen lipopolysaccharide. The mixed lymphocyte response was dose dependently suppressed following CCl4 exposure; however, the delayed-type hypersensitivity response was unaffected. Lymphocyte blastogenesis following mitogenic stimulation with lipopolysaccharide or concanavalin A was also inhibited by CCl4 exposure. These studies demonstrate that exposure to CCl4 results in a marked suppression in both humoral and cell-mediated immune responses at concentrations which also affect the liver as evidenced by the marked increase in SGPT levels.