IVERMECTIN-FACILITATED IMMUNITY IN ONCHOCERCIASIS - ACTIVATION OF PARASITE-SPECIFIC TH1-TYPE RESPONSES WITH SUBCLINICAL ONCHOCERCA-VOLVULUSINFECTION

The present study examined the quantitative and qualitative changes re gistered in the parasite-specific antibody response, cellular reactivi ty and cytokine production profile in onchocerciasis patients repeated ly treated with ivermectin over a period of 8 years. The densities of Onchocerca volvulus microfilariae (mf) in treated patients remained si gnificantly reduced, whereas the number of permanently amicrofilarider mic patients (subclinical infection) increased with repeated treatment s. In vitro cellular responses to O. volvulus antigen (OvAg) were high est (P < 0.01) in untreated control individuals exposed to infection, but negative for mf of O. volvulus (endemic normals). Cellular reactiv ity in repeatedly treated patients was higher at 84 than at 36 months post initial treatment (p.i.t.); furthermore, the proliferative respon ses to OvAg, mycobacterial purified protein derivative (PPD) and strep tococcal SL-O were greater (P < 0.05) at 84 months p.i.t. in amicrofil aridermic than in microfilaria-positive onchocerciasis patients. In am icrofilaridermic patients such reactivity approached the magnitude obs erved in endemic normals. Peripheral blood mononuclear cells (PBMC) fr om patients and endemic normals produced equivalent amounts of IL-2, I L-4 and interferon-gamma (IFN-gamma) in response to mitogenic stimulat ion with phytohaemagglutinin (PHA); in response to OvAg, however, sign ificantly more IL-2 and IFN-gamma were produced by PBMC from subclinic al amicrofilaridermic patients or endemic normals than by mf-positive patients. OvAg-specific production of IL-4 by PBMC from treated patien ts was lower at 84 than at 36 months p.i.t. At three months p.i.t. the titres of circulating OvAg-specific IgG1-3 had increased (P < 0.05), but they then continuously declined with repeated treatments. Only IgG 1 and IgG4 bound to OvAg of mel. wt 2-12 kD at 1 month p.i.t., while r ecognition of OvAg of mel. wt 10-200 kD by IgG1, IgG2 and IgG4 reached a maximum intensity at 3-6 months p.i.t., with the overall intensity of binding to OvAg gradually weakening thereafter. These results sugge st that onchocerciasis-associated immunosuppression is reversible foll owing ivermectin-induced permanent clearance of microfilariae from the skin; and that a vigorous parasite-specific cellular reactivity and a sustained production of IL-2 and IFN-gamma in amicrofilaridermic indi viduals may contribute to controlling O. volvulus infection.