IL6&8 in Malnourished Children With Acute Diarrhea

Cytokines, such as IL-6 and IL-8 can be used as markers of acute infections, including acute gastroenteritis. However, there have been no previous studies on the levels of IL-6 and IL-8 in malnourished children with acute diarrhea. This study aims to evaluate serum levels of interleukins 6 and 8 in malnourished children with acute diarrhea.

Acute gastroenteritis remains a common health problem among children worldwide with significant morbidity, mortality, and economic burden. Diarrheal diseases account for more than half-million deaths of children under 5 years old every year, most of which take place in low- and middle-income countries (LMICs). Moreover, diarrheal diseases are a leading cause of emergency visits and hospitalization. According to the WHO, acute diarrhea is classified into acute watery diarrhea, acute bloody diarrhea (dysentery), persistent diarrhea, and diarrhea with severe malnutrition. Acute watery diarrhea is the most common category in both high and LMICs. Viral infections (e.g., rotavirus, norovirus, adenovirus) are the leading causes of acute watery diarrhea in children (up to 90% of cases), while bacteria (e.g., shigella, salmonella, Campylobacter, enterotoxigenic E. coli) and parasites (e.g., Cryptosporidium, Giardia, and E. histolytica) account for the remainder of cases.

Cytokines can be used as markers of acute infections, including acute gastroenteritis. Interleukin-6 (IL-6) is produced by lymphoid and non-lymphoid cells and plays important role in regulation of immunity, acute-phase response, and hematopoiesis; IL-6 has a well-known role in the defense mechanism in acute gastroenteritis. Interleukin-8 (IL-8) functions in chemotaxis of inflammatory cells, such as neutrophils and lymphocytes, to the site of inflammation, Both IL-6 and IL-8 are critical for immunity against mucosal infections; they are released from the epithelial cells of the gastrointestinal tract to mount its inflammatory responses to infectious agents at local and systemic levels.

Some studies investigated the role of IL-6 and IL-8 as biomarkers for acute diarrhea in children. Results showed significantly increased serum levels of IL-6 and IL-8 in children with acute GE compared with healthy controls. Moreover, IL-6 is significantly elevated in bacterial gastroenteritis in comparison to viral gastroenteritis. However, none of these studies included children with severe acute malnutrition.

Severe acute malnutrition (SAM) is a severe form of malnutrition resulting from inadequate or poor quality dietary intake. This is a serious public health problem, particularly in developing countries. SAM can be classified into marasmus, characterized by overt loss of subcutaneous fat and muscle mass, and Kwashiorkor, characterized by bilateral pitting edema of lower limbs.

Malnutrition is one of the most common causes of impaired immune function in children. Malnutrition leads to defects of phagocytosis, chemotactic function of neutrophils and monocytes, complement system and opsonization, and the function of antigen presenting cells.

As part of its negative impact on immune system, SAM may impair acute phase inflammatory response, including cytokines. In vitro studies showed that peripheral blood mononuclear cells from malnourished children have reduced ability to produce cytokines, such as IL-1, IL-6, IL-8, and tumor necrosis factor alpha. Some studies showed that children with SAM have significantly lower levels of IL-6 and IL-8 compared with healthy controls \[8\]. In contrast, other studies showed similar or higher levels of pro-inflammatory cytokines in malnourished children compared with healthy controls.

To the best of our knowledge, there have been no previous studies on the levels of IL-6 and IL-8 in children with SAM and acute diarrhea.

The aim of this study is to evaluate serum levels of interleukins 6 and 8 in malnourished children with acute diarrhea.

Eligibility Criteria:
Group 1: Cases (Malnourished children with acute diarrhea)

Inclusion Criteria:

* Age: 6 months to 5 years.
* Severe acute malnutrition. Infants and children who are 6-59 months of age and have a mid-upper arm circumference \< 115 mm or a weight for height/length \<-3 Z-score of the WHO growth standards or have bilateral edema.
* Acute diarrhea: Defined according to WHO criteria as the "passage of loose or watery stools at least three times in a 24 h period", lasts less than 14 days, with or without fever or vomiting, but considering the importance of change in stool consistency rather than frequency, and the usefulness of parental insight in deciding whether children have diarrhea or not.

Exclusion Criteria:

* History of antibiotic therapy in the last 72 hours.
* Acute diarrhea in association with systemic infections
* Malignancy
* Chronic diarrhea
* Autoimmune and autoinflammatory diseases.
* Chronic renal/liver failure
* Diabetes mellitus

Group 2: Control (Non-malnourished children with acute diarrhea)

Inclusion Criteria:

* Healthy children aged 6 months to 5 years.
* Acute diarrhea

Exclusion Criteria:

* Malnutrition or obesity
* History of antibiotic therapy in the last 72 hours.
* Acute diarrhea in association with systemic infections
* Malignancy
* Chronic diarrhea
* Autoimmune and autoinflammatory diseases.
* Chronic renal/liver failure
* Diabetes mellitus