CORRELATION BETWEEN TNF PRODUCTION, INCREASE OF PLASMA-C-REACTIVE PROTEIN LEVEL AND SUPPRESSION OF T-LYMPHOCYTE RESPONSE TO CONCANAVALIN-A DURING ERYTHEMA-NODOSUM LEPROSUM

The complex symptoms observed in lepromatous leprosy patients with rea ctive episodes of the erythema nodosum leprosum (ENL) type are associa ted with different serum components actively participating in the acut e inflammatory reaction. Among them are the tumor necrosis factor (TNF ) and the acute-phase protein C-reactive protein (CRP). TNF and CRP we re found at significantly more elevated concentrations in the serum of patients with ENL, with a positive correlation of about 95% when comp ared with patients with nonreactive lepromatous leprosy (L) or tubercu loid leprosy (T) or with control individuals. Furthermore, in another series of experiments CRP had a specific and significant suppressive a ction on concanavalin A (ConA)-induced lymphoproliferation in cultures from patients and controls, the reduction being more marked (75%) in patients with ENL. By extrapolation from its known actions, production of TNF may have a number of potential consequences for the immunobiol ogy of ENL. Thus, TNF may cause direct injury to compromised cells, fa cilitating mononuclear cell activation and production of cytokines suc h as interleukin-1 and interleukin-6, and upregulating hepatocyte expr ession of CRP. Both CRP and TNF in high serum concentrations have the ability to enhance the acute inflammatory process in ENL, favoring inc reased macrophage activation and phagocytosis, and contributing to the elimination of damaged cells and bacilli, as well as in the reduction of T-suppressor cells, with a consequent improvement in the immunolog ic response of ENL patients.