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AB0058 Interferons and Systemic Sclerosis: Correlation Between Interferon Gamma and Interferon-Lambda 1 (IL-29)
  1. A.T. Dantas1,
  2. S.M.C. Gonçalves2,
  3. M.C. Pereira2,
  4. A.R. Almeida2,
  5. C.D.L. Marques1,
  6. M.J.B.D.M. Rego2,
  7. I.D.R. Pitta2,
  8. A.L.B.P. Duarte1,
  9. M.G.D.R. Pitta2
  1. 1Hospital das Clínicas
  2. 2Laboratόrio de Imunomodulação e Novas Aboradagens Terapêtucias Suely Galdino, Universidade Federal de Pernambuco, Recife, Brazil

Abstract

Background Interferon-lambda 1 (IFNl1), also known as Interleukin-29, belongs to the family of type III interferons and is produced by human peripheral blood mononuclear cells (PBMC) and dendritic cells. It was already described antiviral, anti-proliferative and antitumor effects of IFNl1, but immune-regulatory function is still gradually been elucidated. In human T cells, this cytokine was able to inhibit Th2 response by diminishing secretion of IL-4, IL-5 and, mainly, IL-13 but its real role in pathophysiology of human diseases is still unclear.

Objectives To evaluate serum levels of IFNl1 in systemic sclerosis (SSc) patients and healthy controls and its association with Th1 and Th2 cytokines.

Methods Serum samples were obtained from 52 SSc patients (49 women, 3 men) with a mean age of 44.8 years (range 19–79 yrs) and 53 sex and age matched healthy controls. ELISAs for serum levels of IFNl1, IFNg, TNFa, IL-13, IL-2, IL-4, IL-6 and IL-10 were performed with commercially available sandwich ELISA kits, according to the manufacturer's instructions.

Results IFNl1 levels in patients with SSc were significantly higher than those in healthy individuals (24.82±8.78 and 11.04±3.04 pg/ml, respectively; p<0.0001). Also, SSc patients had higher IFNg levels than controls (34.11±8.11 and 10.73±2.77 pg/ml, respectively; p<0.0001). Furthermore, we found a positive correlation between IL-29 and IFNg levels in SSc patients (p=0.0103, r=0.3526). IL-2, IL-4, IL-6, IL-10, IL-13 and TNFa were not detected in most of the patients and normal controls serum. We found that patients with myositis had higher IFNg levels than those without muscle involvement (p=0.0483) but no significant association was found between IL-29 levels and clinical manifestations.

Conclusions IL-29 levels are increased in SSc and are positively correlated with IFNg levels, a Th1 cytokine. Because of its strong inhibitory effect on Th2 pathway demonstrated by previous studies, at this point, we can only speculate on the potential role of IL-29 as an anti-fibrotic cytokine and additional longitudinal studies are needed to evaluate this concern

References

  1. Jordan WJ, Eskdale J, Srinivas S, Pekarek V, Kelner D, Rodia M, Gallagher G.Human interferon lambda-1 (IFN-lambda1/IL-29) modulates the Th1/Th2 response. Genes Immun. 2007 Apr;8(3):254-61.

  2. Srinivas S, Dai J, Eskdale J, Gallagher GE, Megjugorac NJ, Gallagher G. Interferon-lambda1 (interleukin-29) preferentially down-regulates interleukin-13 over other T helper type 2 cytokine responses in vitro. Immunology. 2008 Dec;125(4):492-502.

  3. Wu Q, Yang Q, Lourenco E, Sun H, Zhang Y. Interferon-lambda1 induces peripheral blood mononuclear cell-derived chemokines secretion in patients with systemic lupus erythematosus: its correlation with disease activity. Arthritis Res Ther. 2011 Jun 16;13(3):R88.

Disclosure of Interest None declared

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