Monday, March 23, 2015

IL-3 producing innate B cells drive sepsis susceptibility

Sepsis is a life-threatening condition characterized by over-production of first line defense cytokines such as IL-1β, IL-6, TNF-α (so called cytokine storm) and leading to death due to failure of vital organs (heart, kidney, liver) and coagulation / anti-coagulation systems.

It is not clear whether immune system can defend against sepsis or contrary make it worse. From an evolutionary point of view, sepsis (as infectious overload) would represent dead-end for the host.

However, if we could understand sepsis pathophysiology we can try to manage it. In this regard, new paper in journal Science is of great interest. This study shows that a little known cytokine IL-3 drives host's susceptibility to sepsis.

The authors have studied mouse model of septic shock. They observed that IL-3 KO mice were highly resistant to septic shock

IL-3 KO mice were able to control bacterial counts in the blood.

Reconstitution experiments confirmed that IL-3 was driving sepsis susceptibility.

Additional experiments showed that B cells were the major source of IL-3 during sepsis in this mouse model.

Indeed, adoptive transfer of wild-type B cells into IL-3 KO hosts could increase sepsis susceptibility of the host (though the authors failed to present host survival data in this setting, as in Fig. 1A).

Finally, the authors showed that in humans, survival of sepsis patients correlated with the level of serum IL-3.

In summary, this simple study points to a new therapy for sepsis patients. In would be interesting to know whether reduced innate response in IL-3 KO mice (a) allowed the host to clear the bacteria from the blood using alternative mechanisms (complement, C-reactive protein system, etc) or whether (b) it was easier for IL-3 KO hosts to repair gut wall damage and prevent further leak of gut flora into blood.    

David Usharauli

No comments:

Post a Comment