Endotoxin-induced cytokine and chemokine expression in the HIV-1 transgenic rat

Natasha F Homji,Xin Mao,Sulie L Chang,Erik F Langsdorf

doi:10.1186/1742-2094-9-3

Abstract

BackgroundRepeated exposure to a low dose of a bacterial endotoxin such as lipopolysaccharide (LPS) causes immune cells to become refractory to a subsequent endotoxin challenge, a phenomenon known as endotoxin tolerance (ET). During ET, there is an imbalance in pro- and anti-inflammatory cytokine and chemokine production, leading to a dysregulated immune response. HIV-1 viral proteins are known to have an adverse effect on the immune system. However, the effects of HIV-1 viral proteins during ET have not been investigated.MethodsIn this study, HIV-1 transgenic (HIV-1Tg) rats and control F344 rats (n = 12 ea) were randomly treated with 2 non-pyrogenic doses of LPS (LL) to induce ET, or saline (SS), followed by a high challenge dose of LPS (LL+L, SS+L) or saline (LL+S, SS+S). The gene expression of 84 cytokines, chemokines, and their receptors in the brain and spleen was examined by relative quantitative PCR using a PCR array, and protein levels in the brain, spleen, and serum of 7 of these 84 genes was determined using an electrochemiluminescent assay.ResultsIn the spleen, there was an increase in key pro-inflammatory (IL1α, IL-1β, IFN-γ) and anti-inflammatory (IL-10) cytokines, and inflammatory chemokines (Ccl2, Ccl7, and Ccl9,) in response to LPS in the SS+L and LL+L (ET) groups of both the HIV-1Tg and F344 rats, but was greater in the HIV-1Tg rats than in the F344. In the ET HIV-1Tg and F344 (LL+L) rats in the spleen, the LPS-induced increase in pro-inflammatory cytokines was diminished and that of the anti-inflammatory cytokine was enhanced compared to the SS+L group rats. In the brain, IL-1β, as well as the Ccl2, Ccl3, and Ccl7 chemokines were increased to a greater extent in the HIV-1Tg rats compared to the F344; whereas Cxcl1, Cxcl10, and Cxcl11 were increased to a greater extent in the F344 rats compared to the HIV-1Tg rats in the LL+L and SS+L groups.ConclusionOur data indicate that the continuous presence of HIV-1 viral proteins can have tissue-dependent effects on endotoxin-induced cytokine and chemokine expression in the ET state.

Highlights

Repeated exposure to a low dose of a bacterial endotoxin such as lipopolysaccharide (LPS) causes immune cells to become refractory to a subsequent endotoxin challenge, a phenomenon known as endotoxin tolerance (ET)
Cytokine and chemokine protein expression in the serum, brain, and spleen of Human immunodeficiency virus-1 (HIV-1) transgenic (HIV-1Tg) rats during endotoxin tolerance (ET) The protein levels of IL-1b, KC/GRO, IL-4, IL-5, TNFa, IFN-g, and IL-13 were determined in the brain, spleen, and sera of HIV-1Tg and Fisher/NHsd 344 (F344) rats rendered ET (LL), challenged with either LPS (LL+L) or saline (LL+S), using an electrochemiluminescent (MSD) assay (Table 1, 2, 3)
There was no difference in the basal levels (SS+S group levels) of the cytokines/chemokines measured in the serum in the two strains of animals (Table 1)

Summary

Introduction

Repeated exposure to a low dose of a bacterial endotoxin such as lipopolysaccharide (LPS) causes immune cells to become refractory to a subsequent endotoxin challenge, a phenomenon known as endotoxin tolerance (ET). During ET, there is an imbalance in pro- and anti-inflammatory cytokine and chemokine production, leading to a dysregulated immune response. HIV-1 viral proteins are known to have an adverse effect on the immune system. LPS is a model molecule commonly used to study the inflammatory responses caused by exposure to bacteria, in particular, the induction and actions of inflammatory cytokines and chemokines [4,5,6]. An inflammatory response involves a balance between the production of pro-inflammatory cytokines and chemokines and the subsequent. The Human immunodeficiency virus-1 (HIV-1) is characterized by very rapid viral replication. It is believed that the continued presence of HIV-1 viral proteins plays a role in the clinical progression of HIV-1 infection to full-blown AIDS [22,23,24,25,26]

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Conclusion