To probe the potential role of Th1 versus Th2 reactivity underlying the hygiene hypothesis, intrinsic levels of Th1-associated and Th2-associated antibodies in the serum of wild rodents were compared with that in various strains of laboratory rodents. Studies using rat lung antigens as a target indicated that wild rats have substantially greater levels of autoreactive, polyreactive immunoglobulin G (IgG), but not autoreactive, polyreactive IgM than do laboratory rats, both on a quantitative and qualitative basis. Increased levels of serum IgG and IgE were observed in both wild rats and wild mice relative to their laboratory-raised counterparts, with the effect being most pronounced for IgE levels. Further, wild rats had greater intrinsic levels of both Th1- and Th2-associated IgG subclasses than did lab rats. The habitat (wild versus laboratory raised) had a more substantial impact on immunoglobulin concentration than did age, strain or gender in the animals studied. The presence in wild rodents of increased intrinsic, presumably protective, non-pathogenic responses similar to both autoimmune (autoreactive IgG, Th1-associated) and allergic (IgE, Th2-associated) reactions as well as increased levels of Th1-associated and Th2-associated IgG subclasses points toward a generally increased stimulation of the immune system in these animals rather than a shift in the nature of the immunoreactivity. It is concluded that, at least to the extent that feedback inhibition is a controlling element of immunoreactivity, an overly hygienic environment may affect the threshold of both types of immune responses more so than the balance between the different responses.
