Pesticide exposure promotes disease activity by decreasing lymphoproliferative activity and increasing IL-4 production in systemic sclerosis patients

Background: One of the common findings in systemic sclerosis (SSc) patients has been long-term exposure to environmental toxins such as pesticides. However, the data available shows an equivocal association between pesticide exposure and autoimmunity in SSc.

Methods: We investigated the levels of organochlorine pesticides (OCPs) in blood of 20 SSc patients and 17 healthy controls, and also studied their effect in-vitro on T lymphocytes and their functional responses.

Results: We found higher levels of hexachlorocyclohexane (HCH- α-, β-, and γ) and o,p'-dichlorodiphenyltrichloroethane (DDT) metabolite (p,p΄-DDE) in blood of SSc patients. In vitro treatment of SSc patient PBMCs with either of HCH (100 mM) or DDT (50 µM) caused a significant increase merely in CD8⁺ memory (CD8⁺CD45RO⁺) T lymphocytes. We also observed reduced FoxP3 expression in CD4⁺CD25⁺ (regulatory T cells) of SSc patients. Neither HCH nor DDT exposure of SSc PBMCs altered significantly the secretion of IL-2, IL-10, or IFN-γ, but both of these pesticides elevated their IL-4 (a pro-fibrotic cytokine) secretion.

Conclusion: Taken together, our findings indicate that persistent exposure to these OCPs results in decreased lymphoproliferative activity which promotes disease activity by producing pro-fibrotic cytokine(s). Thus, SSc patients are less able to initiate or augment an immune response to foreign antigens, when there is substantial suppression of lymphocyte function, which increases their susceptibility to infection. Strategies to prevent and control pesticide exposure may play an important role in reducing the morbidity and mortality associated with this disease.