Chemokine regulation of inflammation during acute viral infection.
OBJECTIVE
Chemokines are important inflammatory mediators, and regulate disease due to viral infection. This article will discuss scientific papers published primarily since June 2002 that have introduced new concepts in how chemokines regulate the inflammatory response to specific viruses.


RESULTS
Acute respiratory viruses commonly induce inflammatory chemokines such as CCL3 (also known as macrophage inflammatory protein-1alpha) and CCL5 (RANTES), which can amplify inflammatory responses leading to immunopathology. Where single agent therapy fails, combination antiviral and anti-CCL3 treatment is synergistic and able to prevent mortality in mice infected with the highly lethal pneumonia virus of mice. Human herpesvirus-6 also induces production of CCL3 and CCL5, which are able to block HIV-1 replication in coinfected human lymphoid tissue. On this basis, Margolis has proposed a new and general approach to the treatment and prevention of infection by viral pathogens.


CONCLUSIONS
Inflammatory chemokines play both beneficial and harmful roles in infectious diseases caused by viruses. Blocking them or using them as immunomodulators, depending on the virus, may be rational approaches to treatment or prevention of disease. With regard to blockade, combination antiviral/antichemokine therapy is a new strategy worth considering as a general therapeutic approach to viral infections, including severe acute respiratory syndrome (SARS). With regard to immunomodulation, use of weak or attenuated viruses to skew the local cytokine network to a configuration able to inhibit a pathogen is a new and interesting concept, but is fraught with important safety issues. Identifying master chemokines to target or exploit in human viral infection is a major opportunity and challenge for clinical immunologists.
Glass
William G
WG
Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Rosenberg
Helene F
HF
Murphy
Philip M
PM
D000208:Acute Disease; D020805:Central Nervous System Viral Diseases / Q000188:drug therapy / Q000503:physiopathology; D018925:Chemokines / Q000502:physiology* / Q000627:therapeutic use; D029043:Ebolavirus / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects; D015654:Herpesvirus 6, Human / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology*; D012141:Respiratory Tract Infections / Q000188:drug therapy; D014777:Virus Diseases / Q000188:drug therapy / Q000503:physiopathology*
D018925:Chemokines