Effect of Malnutrition on the Expression of Cytokines Involved in Th1 Cell Differentiation

Abstract

Malnutrition is a common cause of secondary immune deficiency and has been linked to an increased susceptibility to infection in humans. Malnutrition specifically affects T-cell-mediated immune responses. The aim of this study was to assess in lymphocytes from malnourished children the expression levels of IL-12, IL-18 and IL-21, molecules that induce the differentiation of T cells related to the immunological cellular response (Th1 response) and the production of cytokines related to the immunological cellular response (Th1 cytokines). We found that the expression levels of IL-12, IL-18 and IL-21 were significantly diminished in malnourished children compared to well-nourished children and were coincident with lower plasmatic levels of IL-2 and IFN-γ (Th1 cytokines). In this study, we show for the first time that the gene expression and intracellular production of cytokines responsible for Th1 cell differentiation (IL-12, IL-18 and IL-21) are diminished in malnourished children. As expected, this finding was related to lower plasmatic levels of IL-2 and IFN-γ. The decreased expression of Th1 cytokines observed in this study may contribute to the deterioration of the immunological Type 1 (cellular) response. We hypothesize that the decreased production of IL-12, IL-18 and IL-21 in malnourished children contributes to their inability to eradicate infections.

Mortality in children with complicated severe acute malnutrition is related to intestinal and systemic inflammation: an observational cohort study

“…Malnutrition is a common cause of secondary immune deficiency, and previous studies characterizing cytokine changes showed reductions in IL2 (17, 18, 38) and IFNγ (18, 19) with inconsistent reductions in IL1 (38–40) and increases in IL10 (15, 17, 38) and TNF-α (17, 39). Compared with reference ranges (33, 41–44), >50% of patients in our cohort had higher cytokine concentrations for GCSF, IL10, IL12p40, macrophage inflammatory protein 1α, and TNF-α.…”

“…Intestinal function and inflammation in SAM may be modulated by short-chain fatty acids (SCFAs), which are fermentation byproducts produced by the intestinal microflora and are an important energy source for intestinal epithelial cells (11–14). Malnutrition is also associated with altered systemic immune responses, such as abnormal proinflammatory priming (15, 16) decreased regulatory cytokines, and impaired immune activation (17–19). …”

Lymphocyte count as a sign of immunoparalysis and its correlation with nutritional status in pediatric intensive care patients with sepsis: A pilot study

“…The adequate intake of nutrients is essential for organs and systems to function properly; this includes the immune system, whose performance is critical to effectively protect the body against pathogens 6,7.…”

“…Since nutritional deficiencies can lead to immune system dysfunction 7,32, we infer that malnourished patients are more likely to suffer from immunoparalysis. Thus, interventional studies have been performed using nutrient supplementation to reverse this condition </emph>32,33.…”

Protein Energy Malnutrition during Vaccination Has Limited Influence on Vaccine Efficacy but Abolishes Immunity if Administered during Mycobacterium tuberculosis Infection

“…As immunity to TB is mediated by protective T cells, these vaccines employ a range of adjuvants or live-delivery systems to promote protective T cells (reviewed in references 13 and 14). However, the cellular part of the immune system has, in early studies, been reported to be sensitive to the effects of PEM (15,16), resulting in reduced production of the T helper type 1 (Th1) cytokines gamma interferon (IFN-␥) and interleukin-2 (IL-2) (17)(18)(19)(20). The cellular and molecular background of this reduced response is not fully understood and has been the subject of some debate (21)(22)(23)(24)(25).…”