The Interleukin-12 (IL-12)Family: Pivotal Immunoregulatory Cytokines in Malarial Infection

Objective: To review the Interleukin-12 (IL-12) cytokine family in malaria, focusing on its immunoregulatory roles, contribution to disease severity, and potential clinical relevance. Place and Duration of Study: The review was conducted at the Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia from 1st Nov. 2025 to 30th June 2026. Methodology: Relevant literature was reviewed using PubMed, Scopus, Web of Science, and Google Scholar, with emphasis on malaria-specific evidence and key studies describing IL-12 family biology. Results: Malaria induces a tightly regulated inflammatory response in which IL-12 family cytokines help determine parasite control and immunopathology. IL-12 promotes Th1 differentiation and IFN-γ production and is particularly important in early protection. IL-23 supports Th17-associated inflammation, whereas IL-27 has stage-dependent pro- and anti-inflammatory effects. IL-35 is predominantly immunosuppressive and may limit tissue injury while also permitting parasite persistence. The magnitude and timing of these responses vary with parasite burden, hostfactors, and disease stage. Conclusion: An extensive, evidence-based synthesis of the structure, immune role, and importance of the IL-12 family in malaria and considers new research on both humans and animals. The understanding of these cytokines may lead to the development of novel immunotherapeutic strategies and improved malaria control.