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Congress Points Up Newly-Found Uses Of Antibiotics

Despite certain growing difficulties with resistant bacteria, as discussed at length by the 5,000 specialists gathered in Milan, Italy today, antibiotics remain a unique weapon in the battle against infection.

Yet some of the papers presented at the 12th ECCMID (European Congress of Clinical Microbiology and Infectious Diseases) point to new applications of antibiotics, not so much to combat bacteria as to provide immunomodulatory and anti-inflammatory effects.

This is so significant that the Milan Congress has even included in its program a debate on Immunomodulatory Effects of Antimicrobial Drugs.

It is becoming increasingly apparent that certain antibiotics interact with the immune system. In response to infection, the body's natural defenses set off a series of inflammatory-type processes, which, from the physiological point of view, are perfectly normal.

It was recalled at the Congress that a number of laboratory tests have shown that certain antibiotics are in fact able to influence the body's natural responses by modulating the secretion of substances directly involved in the immune reaction, particularly those that play a part in inflammation.

This is true of cytokines, for example. Some cytokines facilitate inflammation, while others reduce it.

Antibiotics can also affect the secretion of certain substances produced by white blood cells, the essential partners to antibiotics' antibacterial action.

When activated, white blood cells normally produce a large quantity of free radicals of oxygen (such as superoxides), which, while they play a role in fighting the infection, may also cause serious damage to surrounding tissue.

"So antibacterial and anti-inflammatory properties are intimately connected and it is difficult to differentiate very clearly between them in vivo at this stage," explains Professor Jos van der Meer, of Nijmegen, The Netherlands, one of the chairs of the debate dedicated to immunomodulatory effects of antimicrobial drugs. "It is also not easy to really delineate what is a beneficial effect in clinical terms. In addition, much of the testing is laboratory-based and many studies have used antibiotic concentrations considerably higher than those applied in clinical practice."

However, things are beginning to change, according to a number of original studies presented at the 12th ECCMID. In addition to their purely scientific interest, they herald potentially practical applications of the immunomodulatory effects of antibiotics.

One of these is the study conducted by Dr. Hisham Ziglam and Professor Roger Finch of Nottingham (United Kingdom), President of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID).

The British team has demonstrated that isoniazid, an antibiotic that has been used exclusively against tuberculosis for almost four decades, reduces the production of free radicals by neutrophils, a type of human white blood cell, as well as the release of certain inflammatory cytokines, such as interleukin-1 alpha and interleukin-10, by monocytes, another type of white blood cell.

Dr. Ziglam told the Congress that "these results could provide a partial explanation of the rapid anti-inflammatory response observed under treatment for tuberculosis."

The team has so far tested over a dozen drugs, notably ciprofloxacin, an antibiotic widely used to treat a large range of common bacterial infections. This drug inhibits the release of all of the cytokines examined during the study, namely interleukin-1 alpha, interleukin-10, interleukin-6 and TNF-alpha.

What is particularly striking is that the results presented in Milan by the British team were obtained using antibiotic concentrations comparable to those applied in clinical practice. They indicate a real, direct modulation of the immune system, which, as Dr. Ziglam is quick to point out, opens up very interesting perspectives.

"The impact of antibiotics on the immune system may be of importance in patients whose immune functions are intact, but it could be much greater in patients with immune deficiencies or immunological disorders," he told the Congress.

The Congress also recalled that, outside the field of infectious diseases, another antibiotic family, the macrolides, has long been known to have an effect on the inflammatory component of asthma. They are now being tested as a treatment of atherosclerosis, where their anti-inflammatory effect appears considerable.

Another anti-tuberculosis drug, rifampicin, has by chance turned out to help symptomatic improvement in patients suffering from rheumatoid arthritis, a typical inflammatory disease.

The specialists gathered at the Congress will not yet venture to suggest that antibiotics could be used tomorrow as anti-inflammatory agents. Nevertheless, the studies presented in Milan demonstrate that this is a new and promising direction of research that could herald original applications of antibiotics, independently of their antibacterial action.

[Contact: Jos van der Meer, Hisham Ziglam]






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