Intestinal parasites infection: protective effect in rheumatoid arthritis? / Parasitoses intestinais: efeito protetor na artrite reumatoide?

Abstract Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, with a progressive course, characterized by chronic synovitis that may evolve with deformities and functional disability, and whose early treatment minimizes joint damage. Its etiopathogenesis is not fully elucidated but comprises immunologic responses mediated by T helper cells (Th1). An apparent minor severity of RA in patients from regions with lower income could be associated with a higher prevalence of gut parasites, especially helminths. Strictly, a shift in the immune response toward the predominance of T helper cells (Th2), due to the chronic exposure to helminths, could modulate negatively the inflammation in RA patients, resulting in lower severity/joint injury. The interaction between the immunological responses of parasitic helminths in rheumatoid arthritis patients is the purpose of this paper.

Resumo A artrite reumatoide (AR) é uma doença inflamatória autoimune, sistêmica, de curso progressivo, caracterizada por exuberante sinovite crônica, que pode gerar deformidades e incapacidade funcional, cujo tratamento precoce minimiza o dano às juntas. Sua etiopatogenia ainda não está completamente elucidada, mas compreende respostas imunológicas com a participação de células T auxiliares (Th1). Uma aparente menor gravidade da AR em pacientes de regiões com menor renda poderia estar associada a maior prevalência de parasitoses intestinais, especialmente as helmintíases. A rigor, um desvio na resposta imune para o predomínio de células T auxiliares (Th2), decorrente da exposição crônica a helmintos, modularia negativamente a inflamação em doentes com AR, e levaria a menor gravidade e dano articular. A revisão de aspectos da influência da reposta imunológica nas parasitoses intestinais, especialmente as helmintíases, em pacientes com artrite reumatoide é o objetivo desse trabalho.

[Th1 and Th2 immune response in hymenolepis nana infection]

Although many experimental studies provide convincing evidence, that type II immunity is protective against helminthes; recent data in mice reveal that Th1 are also important in some cestods like Hymenolepis nana. To reveal the role of Th1 and Th2 lymphocyte in immunity against H.nana, the level of IL12, IFN, IL5, IL13 was determined in serum of human infected with H.nana. In a case control study in 2006 in Mazandaran Medical Sciences University a total of 31 patients [case] with H.nana infection and 30 clinical healthy people [control] were included in this study. Measurment of IL12, IFN, IL13 and IL5 in serum samples were performed by solid-phase sandwich enzyme linked immunosorbant assay. Differential leukocyte count also was done. T test, mannwhitney test and wilcoxan W test were used for data analysis. The mean concentration of IFN, IL13, IL12, IL5 in the sera of patient with H.nana infection were higher than control group, but only the difference between concentration of IFN [P < 0.05] and IL13 [P < 0.05] in two groups were significant. There was an increase in percentage of monocytes, Eosinophils and lymphocytes in patient when compared to the control group, but this increase was not significant. Results form the present study are in agreement with experimental study in that both Th1 and Th2 responses occurs in H.nana infection

The debate over the effector function of eosinophils in helminth infection: new evidence from studies on the regulation of vaccine immunity by IL-12

The production of Th1-type cytokines is associated with strong cell-mediated immunity while Th2-type cytokines are typically involved in the generation of humoral immune responses. In mice vaccinated a single time (1x) with attenuated cercariae of Schistosoma mansoni, the immunity induced is highly dependent on CD4+ T cells and IFN-gamma. In contrast, mice vaccinated multiple times (3x) have decreased IFN-gamma expression, develop a more dominant Th2-type cytokine response as well as protective antibodies which can passively transfer immunity to naive recipients. Previously, we demonstrated the ability of IL-12, a potent IFN-gamma-inducing cytokine to enhance (1x) schistosome cell-mediated immunity when administered during the period of immunization. More recently, we asked what effects IL-12 would have on the development humoral-based immunity. While multiply-immunized/saline-treated mice demonstrated a 70-80 per cent reduction in parasite burden, 3x/IL-12-vaccinated animals displayed an even more striking >90 per cent reduction in challenge infection, which many mice in the later group demonstrating complete protection. Analysis of pulmonary cytokine mRNA responses demonstrated that control challenged mice elicited a dominant Th2-type response, 3x/saline-vaccinated produced a mixed Th1/Th2-type cytokine response, while 3x/saline-vaccinated produced a mixed Th1/Th2-type cytokine response, while 3x/IL-12 immunized animals displayed a dominant Th1-type response. The IL-12-treated group also showed a marked reduction in total serum IgE and tissue eosinophilia while SWAP-specific IgG2a and IgG2b Abs elevated. Interestingly, animals vaccinated with IL-12 also showed a highly significant increase in total Ig titers specific for IrV-5, a known protective antigen. More importantly, 3x/IL-12 serum alone, when transferred to naive mice reduced worm burdens by over 60 per cent while 3x/saline serum transferred significantly less protection. Nevertheless, animals vaccinated in the presence of IL-12 also develop macrophages with enhanced nitric oxide dependent killing activity against the parasites. Together, these observations suggest that IL-12, initially described as an adjuvant for cell-mediated immunity, may also be used as an adjuvant for promoting both humoral and cell-mediated protective responses.