Parasitic helminths tip the balance: potential anti-inflammatory therapies

Parasitic helminths are worms that are classified within the phyla Nematoda (roundworms) and Platyhelminthes (flatworms) (see Table 1). Some nematode species, Filariae being a notable example, are able to coexist with their human host for decades. Interestingly, although millions suffer severe morbidity, a lower incidence of allergy and autoimmune disease has been reported in infected individuals.1,2 Viral and bacterial infections, and autoimmune diseases such as type I diabetes and multiple sclerosis typically induce a T helper type 1 (Th1) pro-inflammatory response producing cytokines such as interleukin-12 (IL-12), interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α). Chronic parasitic helminth infection is associated with high levels of immunoglobulin E (IgE), eosinophilia, mastocytosis and a predominantly Th2 immune response. This Th2 response is characterized by production of IL-4, IL-5, IL-10 and IL-13,3 a cytokine pattern that is also linked to an anti-inflammatory phenotype. There is evidence that a Th2 response is protective in the case of gastrointestinal nematodes.4 However, there is also overwhelming evidence from other helminth infections that a Th2 response may provide an anti-inflammatory regulatory environment.1,5 The counter-regulatory effects of Th1 and Th2 cytokines can be seen in many immune responses and there is strong evidence that the Th2 response generated by helminths can down-regulate Th1 responsiveness to other infections