Immunomodulating effects and hypersensitivity reactions caused by Northeast Indian black fly salivary gland extract

The genus Simulium, black fly (Diptera), comprises >1800 species worldwide, of which 67 species under six subgenera have been well studied in India. While at the extreme, black fly bites can cause onchocerciasis or river blindness, the majority of clinical observations indicate mainly severe pain and continuous itching at bite sites. This investigation experimentally observed that black fly salivary extract (BFSE) causes unique biologic effects including immunomodulation, anti-coagulation, and hypersensitivity reactions in Wistar rats. Salivary glands from black flies were isolated, extracted in saline, and then ≈800 ng extract (BFSE) subcutaneously injected into rats. To evaluate potential immunosuppressive activity of the BFSE, serum levels of interleukins [IL]-6 and -10 and tumor necrosis factor [TNF]-α were assayed. To assess the BFSE impact on coagulation, activated partial thromboplastin time (aPTT), prothrombin time (PT), and bleeding time, as well as generation of coagulation activated factors I, IX, and X were analyzed. Anaphylaxis induction was monitored via electrocardiogram (ECG) and measures of blood pressure and rectal temperature. The data showed that BFSE treatment resulted in a significantly prolonged aPTT, PT, and bleeding time and reversibly inhibited generation of coagulation activated factors I, IX, and X. The extract also led to a prolonged (up to 48 h) suppression of serum IL-6, IL-10, and TNFα production. While these results suggest that BFSE possesses anti-thrombotic, anti-coagulant, and immunomodulatory activities, importantly, they also indicate that the extract has a capacity to induce anaphylaxis and acute cardiotoxicity.