Re: Anti-cytokine therapeutics and infections

[Guest guest]

I worked with Dinarello in the early 1980's at Tufts New

England Medical Center. Interleukin 1 was called leukocytic pyrogen

and LAF back in those days. He was the master of IL-1. I worked on

the project where we cloned the IL-1b gene. Pretty cool stuff in

retrospect.

Tom Brown

> Vaccine. 2003 Jun 1;21 Suppl 2:S24-34.

>

> Anti-cytokine therapeutics and infections.

>

> Dinarello CA.

>

> Department of Medicine, University of Colorado Health Sciences

> Center, Denver, CO 80262, USA.

>

> In view of the increasing use of anti-cytokine-based therapies to

> treat autoimmune diseases, the role of specific cytokines in host

> defense against infection has become a highly relevant area of

> investigation. There are over 300,000 patients worldwide being

> treated with agents that specifically block the biological

> activities of interleukin-1 (IL-1) or tumor necrosis factor (TNF)

> for reducing the severity of autoimmune diseases such as

rheumatoid

> arthritis, Crohn's disease or psoriasis. Those patients receiving

> anti-TNF-alpha or IL-1 blocking therapies are treated on a chronic

> basis. Studies suggest that other chronic inflammatory diseases

will

> benefit from anti-cytokine therapies. However, there is a growing

> body of clinical evidence that neutralization of TNF-alpha is

> associated with an increased risk of opportunistic infections,

> including mycobacterial diseases. Blockade of IL-1 activity with

the

> IL-1 receptor antagonist (IL-1Ra) appears, at present, to be

> relatively safe. However, because of physician under reporting

(some

> estimates of reporting being less than 5% of these infections),

the

> true incidence of infections, both serious and non-serious, will

> remain unknown. Does the increase in infections associated with

anti-

> cytokine-based therapies come as a surprise? Of the two components

> of host defense, the innate and the acquired responses, which are

> affected by anti-cytokine therapies? From a wealth of rodent

studies

> using live infection models, the following conclusions can be

drawn:

> (1) neutralization or gene deletion for TNF-alpha is frequently

> associated with reduction of host defense in models of live Gram-

> positive or Gram-negative infections as well as infection by

> intracellular microbes such as Salmonella and Listeria; (2)

absence

> of the IL-1 receptor can also result in decreased resistance to

> Listeria or Gram-positive bacteria and (3) TNF-alpha and IFN-gamma

> are required for defense against infection caused by Mycobacterium

> tuberculosis.

>

> Publication Types:

> Review

> Review, Tutorial

>

> PMID: 12763679 [PubMed - indexed for MEDLINE]

[Guest guest]

Doesn't it seem almost obvious that if you dampen some aspect of the

immune response (anti-cytokine therapy), for the purpose of reducing

the damage resulting from that immune response, that an effective

substitute or adjunctive therapy would be necessary to prevent

opportunistic pathogens from taking advantage of the situation?

It's only natural that infections will increase if you turn down the

immune system, but it's also a fact that the immune system's

response can be really destructive. Inflammation is an immune

response which can do serious damage to the body when it becomes

chronic (i.e heart disease). It seems kind of crazy to me that

researchers wouldn't automatically realize that anti-cytokine

therapy would have to be accompanied by some kind of anti-microbial

therapy as well. Hopefully, that's the next step in their research

and this is just corroboration of a logical hypothesis.

It also seems to me that anyone researching " autoimmune illness " as

a bonafide illness category, is probably missing a big part of the

microbial picture to begin with. Have they even asked themselves why

there's such an excess in cytokines in these illnesses? Have they

prescreened all of these patients for pre-existing bacterial

imblances?

penny