Alleviation of depressed immunity caused by restraint-stress, by the immunomodulator, lobenzarit disodium (disodium 4-chloro-2,2'-iminodibenzoate).

The immunomodulating effect of lobenzarit disodium (CCA, disodium 4-chloro-2,2'-iminodibenzoate), was examined in restraint-stressed mice which exhibited immunodeficient conditions mainly based on dysfunction of helper T cells. Primary direct plaque-forming cell (PFC) responses to T cell-dependent antigens such as sheep red blood cell (SRBC) and dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH) were severely diminished by restraint-stress, whereas responses to T cell-independent antigens such as DNP-Ficoll (DNP-Fic) and trinitrophenyl-lipopolysaccharide (TNP-LPS) were little reduced and sometimes were even increased. CCA, orally administered to mice at a dose of 50 mg/kg body weight, significantly restored anti-SRBC PFC response. Restraint-stress also markedly decreased the proliferative response of splenic lymphocytes to concanavalin A (Con A), while it slightly augmented the response to lipopolysaccharide (LPS). CCA increased the response to Con A and suppressed the response to LPS. The number of T and B lymphocytes in the spleen were, however, reduced to the same degree by the stress and there was no striking difference in the susceptibility of these two subpopulations of splenic lymphocytes as analysed with fluorescein-activated cell sorter. CCA increased both T and B lymphocytes, but Lyt-1+ (helper/inducer T) cells recovered even more. It is noteworthy that in all these experiments CCA restored the weight of the thymus which is considered to be one of the organs most sensitive to stress. These results indicate that CCA promotes proliferation and differentiation of T cells, especially helper T cells, and restores immune functions depressed by restraint-stress.