The venom of one of Australia’s commonest snakes, the red-bellied black snake, has immunosuppressive effects that make it a potential treatment for rheumatoid arthritis, researchers say.
While better known for its toxic anticoagulant coagulopathy, the venom of the red-bellied black snake also has a unique effect as a modulator of T cell function, scientists at Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, have shown.
In laboratory tests they found that black snake venom suppressed the release of pro-inflammatory cytokines such as interleukin (IL)-2 and tumour necrosis factor (TNF) from human T cells.
The suppression of pro-inflammatory cytokines was dose related and highly potent, with effects equivalent to that seen with standard doses of cyclosporine, the researchers reported in the journal Toxins.
They also noted that the effect on T cells was not associated with cytotoxicity, as there was no inhibition of T cell proliferation or reduction of cell viability, “consistent with an anti-inflammatory mechanism unrelated to the cell cycle.”
Further analysis of the venom identified four fractions responsible for the immunosuppressive activity.
The study investigators said the protein components of the venom include pseudexin isoenzymes A, B, and C, which are basic phospholipase A2 (PLA2) neurotoxins. These proteins have been found in other snake venoms and shown in several studies to have an anti-inflammatory effect – and therefore red-bellied black snake -derived PLA2 may likewise exhibit anti-inflammatory activity.
“Taken together, these data demonstrate the potential for novel medicinal applications of [red-bellied black snake]-derived proteins,” they said.
“These data suggest that compounds from P. porphyriacus venom may be potential drug leads for T cell-associated conditions such as graft versus host disease, rheumatoid arthritis, and inflammatory bowel disease.”
“Given the extent of T cell cytokine suppression observed in our experiments, we recommend investigating the safety and therapeutic efficacy of red-bellied black snake and pure toxins in animal models of disease including the T cell transfer (TcT) model of colitis, FCA-induced arthritis, SLE, or skin allograft rejection,” they concluded.