Soluble IL-4 receptor, potential for therapeutic and prophylactic intervention

Many bacterial, protozoal and viral infections trigger a cell-mediated immune response. Of special importance for the clinical outcome of disease, however, is the relative predominance of T helper (Th) cell populations (Th1 and Th2) secreting different patterns of lymphokines. Preferential development of one Th subset occurs apparent at the early stages of an infection, suggesting that the mechanisms driving the immune response in one direction or the other operate soon after exposure to the antigen. Cytokines are among the most important factors regulating T cell differentiation and expansion of the different T cell subtypes. As in experimental candidiasis, listeriosis, yersiniosis and murine retrovirus induced immunodeficiency syndrome (MAIDS), interleukin-4 (IL-4) is of central importance also for the clinical course of murine cutaneous leishmaniasis. It has been demonstrated that the presence of IL-4 is essential for the development of disease promoting Th2 cells whereas neutralization of IL-4 in vivo led to establishment of protective immunity against leishmania. A naturally occurring antagonist of IL-4 is the soluble IL-4 receptor (sIL-4R), which retains its ligand binding properties and binds IL-4 with high affinity. We therefore examined the immunomodulatory and therapeutic capacity of recombinant sIL-4R in murine cutaneous leishmaniasis. BALB/c mice were treated with recombinant sIL-4+ during the onset of the immune response. This treatment rendered BALB/c mice clinically resistant to Leishmania major (L. major), led to reduced parasite load, shifted the pattern of cytokines towards Th1 type and provided durable resistance against reinfection with L. major.(ABSTRACT TRUNCATED AT 250 WORDS)