| Abstract: | Helminth infections have been associated with protection against allergy and autoimmune diseases. We investigated the effects of chronic infections with Ascaris lumbricoides and Trichuris trichiura (measured twice over a 5-year period) on cytokine and antibody responses. We collected blood from 1,060 children aged 4 to 11 years living in a poor urban area of Brazil and measured Th1 (gamma interferon [IFN-γ]) and Th2 (interleukin-5 [IL-5] and IL-13) cytokines and the regulatory cytokine IL-10 in unstimulated and stimulated (with mitogen or A. lumbricoides antigens) cultures of peripheral blood leukocytes and levels of total IgE and anti-A. lumbricoides IgG4 and IgE in serum. Intestinal helminth infections were associated with an increased proportion of children producing IL-5 in response to A. lumbricoides and producing IL-10 spontaneously, especially among coinfected and chronically infected children. Helminth infections were associated with a generalized suppression of cytokine responses to mitogen. Levels of total IgE and anti-A. lumbricoides IgG4 and IgE were especially elevated in chronically infected children. In conclusion, intestinal helminth infections were associated with a typical Th2 immune response profile and with the induction of immune hyporesponsiveness that was associated with greater frequencies of the production of spontaneous IL-10.Among infectious agents, helminth parasites are regarded as master manipulators of the host immune response, being associated with chronic but generally asymptomatic infections. Although helminth infections induce strong Th2 responses, parasitic worms may survive in their mammalian hosts by switching off inflammatory immune responses and inducing a tolerant response to parasite antigens (38).Atopy, characterized by raised immunoglobulin E (IgE) levels, is considered a major mediator of allergic diseases such as asthma, rhinoconjunctivitis, and eczema. The interaction of an environmental allergen with the innate immune system, uptake by antigen-presenting cells, and subsequent T-cell priming lead to the stimulation of Th2 cytokines, such as interleukin-4 (IL-4), IL-5, and IL-13. These cytokines stimulate IgE production and increased numbers of eosinophils and mast cells, which together may cause allergic inflammation in the respiratory tract (37).The hygiene hypothesis has tried to explain the temporal trends of increased allergic disease prevalence over recent decades in industrialized countries by alterations in the host response to environmental allergens caused by decreased exposure to childhood infections through improvements in hygiene and greater access to antibiotics and vaccines (32). Such improved hygiene has been considered to alter the balance between type 1 (Th1) and type 2 (Th2) immune responses due to a failure of immune regulation resulting in allergy-mediating Th2 responses (22).Exposure to pathogens and their products, and to helminths in particular, has been shown to protect against the development of autoimmune and allergic diseases in experimental animal models (7, 8, 10, 23, 25, 26, 28), and some evidence in support of this has been observed in human populations (3, 8, 10, 23, 29, 30, 31).We previously demonstrated that children living in circumstances of poor hygiene without access to sanitation or clean water during the first 3 years of life have elevated spontaneous production of IL-10 up to 8 years later in life (13).In the present study, we compared cytokine profiles from whole-blood cultures and antibody responses among children stratified by intestinal helminth infection status, determined at two separate time points in childhood. |
