Ivermectin-facilitated immunity in onchocerciasis. Reversal of lymphocytopenia, cellular anergy and deficient cytokine production after single treatment

Abstract

A longitudinal investigation has been conducted into the cell-mediated immune responses of onchocerciasis patients after a single-dose treatment with ivermectin. Untreated patients tested for delayed cutaneous hypersensitivity (DCH) to seven recall antigens showed lower responses than infection-free control individuals (P in vitro cellular reactivity to Onchocerca volvulus-derived antigen (OvAg) was reduced in untreated patients as compared with controls, and the lymphocyte blastogenic responses to OvAg and streptolysin-O clearly improved up to 14 months after treatment. Peripheral blood mononuclear cells (PBMC) from untreated patients produced IL-Iβ, tumour necrosis factor-alpha (TNF-α) and IL-6 in response to mitogenic stimulation with phytohaemagglutinin (PHA), only low levels of IL-Iβ, IL-2 and TNF-α in response to OvAg, but higher amounts of IL-4 and interferon-gamma (IFN-γ) in response to OvAg than control individuals. After ivermectin treatment, the OvAg-induced production of IL-1β and TNF-α increased significantly I 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-γ 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 + cells and a significantly smaller CD4⁺/CD8⁺ cell ratio as compared with controls. By 4 weeks after treatment and thereafter, CD4⁺ T cells increased relatively and absolutely (P +CD45RO⁺) and a temporarily improved CD4⁺/ CD8⁺ cell ratio (P=0.001). The expression of the low-affinity receptor for IgE (CD23) on total lymphocytes decreased from 14% to 7% by 14 months after treatment. The CD8⁺ cells and CD3⁺TCRγδ⁺ cells were higher in patients than in controls and both remained elevated until 14 months after treatment. These results suggest a distinctly improved cellular immunity in human onchocerciasis that was facilitated by ivermectin therapy.