Acceleration of viral replication and up-regulation of cytokine levels by antimalarials: implications in malaria-endemic areas

• Published in: The American journal of tropical medicine and hygiene Vol. 61; no. 2; pp. 180 - 186
• Main Authors: Seth, P, Mani, H, Singh, AK, Banaudha, KK, Madhavan, S, Sidhu, GS, Gaddipati, JP, Vogel, SN, Maheshwari, RK
• Format: Journal Article
• Language: English
• Published: Lawrence, KS ASTMH 01.08.1999; Allen Press
• Subjects: Alphavirus Infections - pathology; Alphavirus Infections - virology; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - adverse effects; Antimalarials - pharmacology; Antiparasitic agents; Biological and medical sciences; Chloroquine; Female; Interleukin 1 receptor antagonist; Interleukins - biosynthesis; Interleukins - genetics; Lethal Dose 50; Male; Medical sciences; Mice; Mice, Inbred BALB C; Pharmacology. Drug treatments; RNA, Messenger - drug effects; RNA, Messenger - genetics; Semliki Forest virus; Semliki forest virus - drug effects; Semliki forest virus - physiology; Tropical medicine; Up-Regulation; Virus Replication - drug effects; Asia; India; Semliki forest virus; Antimalarial; Rodentia; Togaviridae; Experimental study; Virus; Vertebrata; Chemotherapy; Mammalia; Treatment; Mouse; Animal; Alphavirus; Complication; Replication; Acceleration; Comparative study
• ISSN: 0002-9637; 1476-1645
• DOI: 10.4269/ajtmh.1999.61.180

Antimalarial drugs are widely used in malaria endemic areas, both for chemoprophylaxis and also empirically to treat patients presenting with fever. Previously, we have reported that chloroquine enhances the severity of Semliki forest virus (SFV) and encephalomyocarditis virus infection. The studies presented herein show that a broad spectrum of antimalarial drugs augmented the replication of SFV in mice, concomitant with greater tissue damage and up-regulation of mRNA levels of various inflammatory cytokine genes, including interleukin-1 receptor antagonist (IL-1Ra), II-1alpha, IL-1beta, IL-6, IL-12p40, and interferon-gamma inducing factor. Furthermore, chloroquine enhances IL-1Ra production in RAW cells in vitro. Since IL-1Ra is known to be up-regulated in a number of viral infections, we propose that a further enhancement of its expression by antimalarials may be responsible for the increased severity of viral infection in our studies. Thus, the widespread use of antimalarials in malaria-endemic areas may predispose the population to viral infections. Further studies are in progress to delineate mechanism(s) involved in cytokine up-regulation and acceleration of viral replication.