A systematic review of circulating IP-10/CXCL10 in patients with Plasmodium infections in relation to disease severity

Abstract

Interferon γ-induced protein 10 kDa (IP-10) or C–X–C motif chemokine 10 (CXCL10) is produced and secreted from specific leukocytes such as neutrophils, eosinophils, and monocytes, which play key roles in the immune response to Plasmodium infections. This systematic review aimed to collate and critically appraise the current evidence on IP-10 levels in malaria patients. It provided insights into its role in malaria pathogenesis and potential as a biomarker for Plasmodium infections and disease severity. The protocol for this systematic review was registered in PROSPERO (number CRD42024556087). A comprehensive literature search was conducted across multiple databases, including Embase, PubMed, Scopus, Ovid, ProQuest, and MEDLINE, to identify relevant studies examining the role of IP-10 in patients with Plasmodium infections. A narrative synthesis was applied to summarize key findings and to provide an overview of the relationship between IP-10/CXCL10 levels and Plasmodium infection and disease severity. A total of 1933 records were identified, and 26 studies were included in the synthesis. The studies collectively indicated that IP-10 levels are elevated in patients with Plasmodium infections compared to healthy or non-malarial controls. Most studies reported that increased IP-10 levels were associated with increased disease severity. However, a few studies found no significant difference or decreased levels in patients with severe Plasmodium infections compared to those with uncomplicated or mild malaria. Additionally, several studies indicated that IP-10 levels were elevated in cerebral malaria. The systematic review suggests that IP-10 is elevated in patients with Plasmodium infections. However, the variability in findings across different studies regarding the association between IP-10 and severe malaria, particularly cerebral malaria, highlights the need for further comprehensive studies. Addressing confounding factors will be crucial in future research to better understand the role of IP-10 in Plasmodium infections and the pathogenesis of severe disease.