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Ivermectin-facilitatedimmunityinonchocerciasis. Reversal of lymphocytopenia, cellular anergy and deficient cytokine productionaftersingletreatment

P. T. SOBOSLAY, et al.

A longitudinal investigation has been conducted into the cell-mediated immune responses of onchocerciasispatientsafterasingle-dosetreatmentwithivermectin.Untreatedpatientstestedfor delayed cutaneous hypersensitivity (DCH) to seven recall antigens showed lower responses than infection-freecontrolindividuals(P<0-01),but6and14monthsaftertreatmentDCH reactions increasedtosimilarlevelstothoseseeninthecontrols.TheinvitrocellularreactivitytoOnchocerca volvulus-derived antigen (OvAg) was reduced in untreated patients as compared with controls, and thelymphocyteblastogenicresponsestoOvAgandstreptolysin-Oclearlyimprovedupto14months aftertreatment.Peripheralbloodmononuclearcels(PBMC) fromuntreatedpatientsproducedIL- If, tumour necrosis factor-alpha (TNF-a) and IL-6 in response to mitogenic stimulation with phytohaemagglutinin (PHA), only low levels of IL-Ifl, IL-2 and TNF-a in response to OvAg, but higheramountsofIL-4andinterferon-gamma(IFN-y)inresponsetoOvAgthancontrolindividuals. After ivermectin treatment, the OvAg-induced production of IL-I# and TNF-a increased significantly 1 and 14 months after treatment. The PHA-induced production of IL-2 and IL-4 increased 1 month after treatment and remained significantly elevated until 14 months after treatment, whereas the OvAg-specific secretion of IL-2, IL-4 and IFN-y did not change after ivermectin treatment. Flow cytometric analysis of lymphocyte-subsets in the peripheral blood of untreated patients revealed a relative and absolute (P<0-01) diminution of CD4+ cels and a significantlysmallerCD4+/CD8+ celratioascomparedwithcontrols.By4weeksaftertreatment andthereafter,CD4+ T celsincreasedrelativelyandabsolutely(P<001);likewisetherewasan absoluteincreaseinT-helper-inducercels(CD4+CD45RO+) andatemporarilyimprovedCD4+/ CD8+ celratio(P=0001).Theexpressionofthelow-affinityreceptorforIgE(CD23)ontotal lymphocytes decreased from 14% to 7% by 14 months after treatment. The CD8+ cels and CD3+TCRyb+ celswerehigherinpatientsthanincontrolsandbothremainedelevateduntil14 months after treatment. These results suggest a distinctly improved cellular immunity in human onchocerciasis that was facilitated by ivermectin therapy.

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