[Inflammatory cascade response to toxin release: therapeutic perspectives]

Release of toxins in the organism trigger a cascade of biological and chemical events. The process involves a large number of molecules produced under genetic control in a perfectly regulated chronological order. Certain molecules (TNFx, IL-1, Il-2.) have inflammatory proprieties, generally producing systemic Inflammatory Response Syndrome (SIRS). Other less numerous molecules (IL-4, IL-10) have antiinflammatory actions. Finally, soluble receptors and these cytokines contribute to the decrease in the quantity of active cytokines at the receptor level. Dozens of other molecules, many of which remain to be fully understood, are also found in the blood stream. They can, for example, facilitate white cell adhesion (ICAM, VCAM, selectins.). Some of them (G-CSF. CM-CSF. IL-5) stimulate production of granulocytes, monocytes, eosinophils. More recently, certain peptides, like macrophage inhibiting factor (MIF) and procalcitonin (PCT) have been added to the list of molecules involved in bacterial infections. Coagulation factors are also very rapidly released in response to toxinic aggression triggering disseminated intravascular coagulation. Later, acute-hase inflammation proteins, such as C-reactive protein (CRP), haptoglobin, serum amyloid A, etc. are found in largely increased quantities. All these molecules are potential markers of inflammation. Only a few have however been retained for routine assay due to their fragility and their short-half life or due to analytical difficulties. CRP and PCT can however be used to differentiate viral infections from bacterial infections and are thus routinely used in clinical applications. In the second part of this review, we briefly discuss therapeutic perspectives for severe infections and septic shock. There have been many attempts to neutralize different cytokines but results have been disappointing to date. There are however many possibilities currently under study, particularly neutralization of endotoxins, immunomodulation, use of recombinant C and S proteins, etc.