We did an extensive Medline search of publications from 1985 until January, 2005. Only English language papers were considered. Search terms included “IL-10”, “IL-10 and hepatitis B virus”, “IL-10 and hepatitis C virus”, “IL-10 and Epstein Barr virus”, “IL-10 and cytomegalovirus”, “IL-10 and human immunodeficiency virus”, “IL-10 and tuberculosis”, “IL-10 and Mycobacterium”, “IL-10 and Leishmaniasis”, “IL-10 and Helminths”, “IL-10 and Coxiella burnetii”, and “IL-10 and Bartonella”. We also
ReviewThe two faces of interleukin 10 in human infectious diseases
Introduction
Resolution of infections depends on the host's ability to mount a protective immune response mainly based on the recruitment of immunocompetent effectors and the establishment of immune memory. When immune response is impaired, as exemplified by primary and secondary immunodeficiencies, infections are no longer controlled. However, exacerbated responses to infectious diseases induce tissue or systemic lesions, which may be deleterious to the patient. In other words, immunoregulatory mechanisms are necessary to shape the amplitude of immune response and to prevent infection-associated lesions. Interleukin 10 is a critical immunoregulatory molecule. It is a member of an expanding family consisting of cellular and viral cytokines. Its cellular version is produced by myeloid cells, B cells, and as more recently reported, by regulatory cells. Many bacteria, viruses, parasites, or their products are able to stimulate production of interleukin 10 by host cells. Viral versions of the molecule are believed to act as a molecular decoy leading to immune evasion. Interleukin 10 acts as a multifunctional cytokine in human infectious diseases. By disarming innate as well as adaptive responses, it creates favourable conditions for the persistence of microbes and chronic infectious diseases. However, controlling the immune response is also important because it prevents reactivity to self-antigens and attenuates exaggerated immune response that can lead to deleterious tissue lesions. Although much research has described the regulatory effects of interleukin 10 in vitro and in animal models of infection, its role in clinical situations has yet to be elucidated. Our purpose is to provide new insight into the role of interleukin 10 in primary and secondary infections through analysis of clinical situations.
Section snippets
Structure, production, and functions
Interleukin 10 belongs to the class II family of α-helical cytokines that is composed of the type I interferons, interferon γ, and interleukin 10. The main structural feature is a left-handed anti-parallel four-helix bundle.1, 2 The cellular subfamily of the molecule includes interleukin 10, initially described as cytokine synthesis inhibitory factor, and five paralogues named interleukins 19, 20, 22 (interleukin-10-related T cell derived inducible factor), 24 (melanoma
Susceptibility to primary infections
Interleukin 10 increases host susceptibility to numerous intracellular microorganisms such as Mycobacterium bovis (Calmette-Guérin bacillus) and environmental mycobacteria (Mycobacterium avium) in animal models because reducing the amount of interleukin 10 improves resistance to infection and increasing it impairs resistance to infection. These findings have been exhaustively reviewed (table 1).9 Interleukin 10 increases host susceptibility to extracellular bacteria such as Streptococcus
Microbial persistence and evolution of infectious diseases
Interleukin 10 is clearly involved in the persistence of bacteria in hosts via the induction of an anergic state and, consequently, in the evolution of infectious diseases. By contrast with its role in susceptibility, numerous clinical reports support the role of interleukin 10 in the evolution of infectious diseases (table 2). One example is Q fever, an infectious disease due to Coxiella burnetii. Q fever is characterised by a primary infection that is often asymptomatic and may become chronic
Protection in infection-mediated tissue injuries
In the preceding sections, we have shown that interleukin 10 is involved in the evolution of infectious diseases and consequently compromises health through host immunosuppression. However, like the two-faced Roman god Janus, interleukin 10 may protect hosts from exaggerated inflammatory and immune reactions and tissue injuries secondary to acute or chronic infections. This is illustrated by interleukin-10-deficient mice that develop colitis triggered by commensal flora.123 Interleukin 10 also
Infections and atopy
The hygiene hypothesis states that improved hygiene and public health measures along with the use of vaccines and antibiotics have reduced the incidence of infections but have also increased the number of inflammatory diseases including asthma, atopy, inflammatory bowel disease, and multiple sclerosis in developed countries.173, 174 There is an inverse relationship between bacterial (M tuberculosis, H pylori), viral (measles, hepatitis A), and protozoan (Toxoplasma gondii) infections that
Conclusions
Our review reveals a major role for interleukin 10 in two features of infectious diseases. First, although interleukin 10 is dispensable for human susceptibility to intracellular pathogens, it is closely associated with microbial persistence by interfering with innate and adaptive protective immunity. Blocking systemic interleukin 10 may be an attractive therapeutic approach but using antibodies to interleukin 10 increases the risk of autoimmunity or inflammatory disorders. Second, interleukin
Search strategy and selection criteria
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