Trends in Immunology
Volume 23, Issue 8, 1 August 2002, Pages 403-408
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Review
GM-CSF in inflammation and autoimmunity

https://doi.org/10.1016/S1471-4906(02)02260-3Get rights and content

Abstract

Granulocyte macrophage-colony stimulating factor (GM-CSF) is now best viewed as a major regulator governing the functions of granulocyte and macrophage lineage populations at all stages of maturation. There is recent evidence for a key role for GM-CSF in inflammatory and autoimmune diseases, therefore making it worthy of consideration for targetting. Such evidence includes disease exacerbation following its administration and amelioration of disease in animal models by GM-CSF gene targetting or by anti-GM-CSF antibody blockade. The interdependence of GM-CSF formation and that of the important proinflammatory cytokines, interleukin-1 and tumour necrosis factor-α (TNF-α), is discussed, as is the greater disease suppression found in arthritis models following GM-CSF depletion compared with that observed in the absence of TNF-α.

Section snippets

What are the responses to administered GM-CSF?

Several studies have monitored cellular changes and inflammatory responses following in vivo GM-CSF administration. Systemic or intraperitoneal GM-CSF injection in mice led to increased numbers of both circulating neutrophils and cycling peritoneal macrophages [11], as well as the development and differentiation of CD5? macrophages in the peritoneal cavity. GM-CSF rapidly primes mice for enhanced proinflammatory cytokine production in response to LPS and tumour necrosis factor-α (TNF-α) [12].

What are the in vitro responses to GM-CSF and which cells produce it?

Numerous examples of the in vitro action of GM-CSF on monocytes or macrophages, granulocytes and eosinophils have now been reported and only a few pertinent examples consistent with possible proinflammatory actions will be given. There is debate as to the extent of the direct induction of certain inflammatory mediators by GM-CSF-treated monocytes or macrophages [25]. Some data indicate that GM-CSF can induce the secretion of inflammatory cytokines [e.g. interleukin-1 (IL-1) and TNF-α], whereas

Is GM-CSF targetting effective in inflammation and autoimmunity?

Neither the presence of GM-CSF at sites of inflammation nor the elicitation of an inflammatory response by exogenous GM-CSF necessarily demonstrates that it is crucial to the progression of inflammatory reactions. Based in part on the evidence for the proinflammatory actions of GM-CSF and its increased production following IL-1 and TNF-α treatment by several cell types, we and others have proposed that GM-CSF allows communication between hemopoietic cells and local tissue cells during

Conclusions and unanswered questions

The precise mechanism(s) involved in the proinflammatory effect of GM-CSF in disease are yet to be defined. It is likely that GM-CSF has a central role in the local activation, recruitment and survival of macrophage lineage cells and PMNs, perhaps even contributing to macrophage proliferation at sites of inflammation (see, for example, [58]). Its role could extend both to the initiating and effector phases of disease; in addition, it could even function systemically. More information is needed

Acknowledgements

This work was supported by grants from the National Health and Medical Research Council of Australia. R. Sallay is thanked for typing the manuscript.

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