Leukocytes Of Patients With Schistosoma Mansoni Respond With A Th2 Pattern Of Cytokine Production To Mitogen Or Egg Antigens But With A Th0 Pattern To Worm Antigens

Abstract

Cytokine responses of peripheral blood mononuclear cells from humans infected with Schistosoma mansoni were assessed. By ELISA and ELISPOT, persons with acute and hepatosplenic infections produced higher levels of interleukin (IL)-4 and IL-5 and higher frequencies of IL-4-producing cells in response to mitogen than did uninfected persons. In contrast, mitogen-induced production of the Th1 cytokine interferon-gamma (IFN-gamma) did not differ from that of uninfected controls. Upon stimulation with egg antigens, many patients responded with elevated IL-4 mRNA levels but displayed no appreciable increases in Th1 (i.e., IFN-gamma and IL-2) cytokine transcripts. Nevertheless, in cells stimulated with adult worm antigen, a more mixed Th0-type response was observed with production of both Th1 and Th2 cytokines. These results support previous findings in laboratory mice that schistosome infection results in increased production of Th2 cytokines. Unlike mice, infected humans do not display a generalized down-modulation in Th1 responses but instead show a selective deficiency in IFN-gamma and usually IL-2 responses to egg antigens.

Specific situations related to acute schistosomiasis in Pernambuco, Brazil

“…The same happened with IL-5, stimulated by SEA suggesting that the cytokine profile in acute patients is characterised by a mixed type 1 and 2 response. This, is in agreement with Williams et al (1994), showing that patients with an acute form of illness respond to specific antigens with hight cytokine levels, resulting in a mixed type 1 and 2 response (type 0) (Montenegro et al 1999) In four patients, due to the intensity of the symptoms, it was necessary to prescribe cortisone at a dosage of 0.5 mg/kg for the first two weeks until the symptoms disappeared. All infected subjects were treated three months after the infection with oxamniquine at a dosage of 15 mg/kg.…”

“…Six patients were submitted to more detailed immunological tests and showed higher IFN-γ , IL-4 and IL-5 levels than patients with chronic forms of schistosomiasis (Williams et al 1994).…”

Microbial Compounds Selectively Induce Th1 Cell-Promoting or Th2 Cell-Promoting Dendritic Cells In Vitro with Diverse Th Cell-Polarizing Signals

“…Soluble egg Ags (SEA) of the helminth Schistosoma mansoni and the toxin of the intestinal bacterium Vibrio cholerae (CT), both associated with Th2 cell responses (13,14), as well as dsRNA (poly(I:C), a mimic of viral RNA) and the toxin of the intracellular bacterium Bordetella pertussis (PT), both associated with Th1 cell responses (15), all promoted sentinel DCs to develop into functional effector cells with stably polarized DC2 or DC1 phenotypes, respectively. It became clear that, although the effector DC1 or DC2 populations induced similar Th1 and Th2 cell subsets, there is a heterogeneity within DC1 and DC2 subsets with respect to the expression and use of Th-polarizing molecules.…”

Preliminary results on the effects of CD40/CD40L interactions and SAC-induction on IFN-gamma expression in human schistosomiasis

“…Th2 cytokines inhibit macrophage activation (Oswald et al 1992) and have been implicated in granuloma formation around tissue deposited eggs (Chensue et al 1992, Wynn et al 1993. In human studies it was noted an impaired balance of Th2 and Th1 cytokine production (Williams et al 1994), suggesting there is not a global suppression of Th1 response in humans but it is possible that the nonsynchronous nature of human infections which often stem from multiple parasite may obscure any Th1 cytokine response (Mahanty et al 1992, Ribeiro de Jesus et al 1993, King et al 1993.…”

“…The supernatants were collected at 96 h and stored at -70 o C for subsequent determination of cytokine production. The measurement of IFN-γ cytokines was performed by ELISA using specific capture and detection mAbs following previously published protocols (Williams et al 1994, Montenegro et al 1999). All statistical comparisions were made by use of a paired student t test or, for unpaired data, the student t test for independent samples.…”