Immunomodulation of serum complement (C3) and macrophages by synthetic pyrethroid fenvalerate: in vitro study

Fenvalerate, a type II synthetic pyrethroid, has emerged as one of the most potent indoor toxicants. Despite its widespread usage, the adverse effect of this insecticide on immune defense mechanism has not been comprehensively investigated. In this in vitro study we report the effect of fenvalerate on two pivotal components of the immune network, namely the complement system and macrophages. Fenvalerate treated human sera showed serum complement activation as evident by significant (p<0.05) increase in C3b, C3d and C3a levels and a significant (p<0.05) decline in CH50 levels. Further detailed study demonstrates that the activation of complement system is through alternative pathway. This is possibly responsible for various allergic manifestations often reported in subjects exposed to fenvalerate. In addition, fenvalerate induce cellular apoptosis and cytotoxicity, as demonstrated by cytoplasmic vacuolization, heterochromatin condensation, hypodiploid nuclei and DNA fragmentation in macrophages. Considerable deleterious effects on macrophages in conjunction with uncontrolled serum complement activation are probably one of the major mechanisms contributing for the immunosuppressive effects of fenvalerate.