Interleukin-7 and interleukin-12 have different effects in rescue of depressed cellular immunity: Comparison of malignant and tuberculous pleural effusions

[[abstract]]The present study attempts to determine the role of interleukin-7 (IL-7) and IL-12 in recovering the functions of the lymphocytes of malignant effusion, in terms of cytokine production, proliferation, and cytolytic activity, compared with lymphocytes from tuberculous pleural effusion. Effusion-associated lymphocytes (EAL) were isolated from tuberculous (tEAL) and malignant (mEAL) pleural effusions. The EAL proliferate response was measured after 3 days in culture. Interferon-gamma (IFN-gamma) production and cytotoxicity against K-562 cells or autologous tumor cells were assessed after 6 days in culture. It was found that the mEAL had depressed proliferation, IFN-gamma production, and cytolytic activity, as compared with tEAL. Stimulation with IL-12 plus IL-2, but not with IL-7 plus IL-2, fully restored the IFN-gamma production of mEAL to that of tEAL levels. In contrast, the proliferate response of mEAL was enhanced significantly more with IL-7 plus IL-2 than with IL-12 plus IL-2. Both the IL-7 plus IL-2 and IL-12 plus IL-2 stimulation of mEAL showed a significant increase in cytolytic activity against autologous tumor cells, although the cytolytic activity against K-562 cells did not increase. These results suggest that tEAL had a higher cellular activity than mEAL. This depressed cellular function of mEAL could be reversed with cytokines. However, different cytokines had different effects on mEAL; for example, IL-7 had a better effect in the stimulation of lymphocyte proliferation compared with IL-12, which had a better effect in driving the lymphocytes to the T helper 1 (TH1) pathway and a higher IFN-gamma production. Both IL-7 and IL-12, in the presence of IL-2, can restore the immunosuppressed cytolytic activity of the lymphocytes of malignant pleural effusion against autologous tumor