initiatives such as the surviving sepsis campaign , launched in 2002 as a collaborative initiative of the european society of intensive care medicine , the international sepsis forum , and the society of critical care medicine , aim to effectively reduce risk of death from severe sepsis and septic shock . nonetheless , although substantial benefits raised from the implementation of this campaign have been obtained , much work remains if we are to realise the full potential promised by this strategy . recently , new treatment approaches based on interventions for coagulation or inflammation have failed to improve survival in sepsis . a deeper understanding of the processes leading to sepsis is necessary before we can design an effective suite of interventions . dysregulation of the immune response to infection is acknowledged to contribute to the pathogenesis of the disease . critical illness itself , surgery and concomitant comorbidities such as diabetes , chronic renal failure or chronic obstructive pulmonary disease affect host responses to infection , which could in turn facilitate the development of sepsis or impair outcome once sepsis is established . despite these precedents , the potential role of immunological monitoring in this disease has not been appropriately considered to the present moment . for years , two phases have been described in sepsis : an initial systemic inflammatory response syndrome followed by the negative feedback of a secondary compensatory anti - inflammatory response syndrome . in contrast to this long - held view , marchant and colleagues and our group have observed that production of the immunosuppressive cytokine il-10 occurs from the very first hours following the diagnosis of severe sepsis or septic shock , and that it is directly associated with the secretion of proinflammatory cytokines [ 7 - 9 ] . levels of igg , igm and iga at diagnosis have been reported to correlate directly with survival . in turn , nonsurvivors have lower levels of c4 ( a protein of the complement system ) than survivors . natural killer cell counts and function also seem to have an important role in this disease . severe depletion of immune effector cells is a universal finding in all age groups during sepsis . quantification of lymphocyte subsets and evaluation of their function could thus have diagnostic and prognostic value in sepsis . at the genomic level , repression of networks corresponding to major histocompatibility complex antigen presentation cumulative evidence supports the notion that the immunological situation of the patient is linked to the final outcome in sepsis . immunological monitoring could thus contribute to the prevention or the treatment of sepsis in a personalised and timely manner . interestingly , there is no currently available information on the potential role of proper immunological monitoring for the prevention of sepsis . immunological monitoring could help to identify patients with immunological deficiencies ( secondary to their disease process , treatment , and so forth ) at higher risk for developing community acquired or nosocomial sepsis . periodic monitoring of patients hospitalised in key services ( that is , oncology , transplantation units , critical care units ) could help to identify specific humoral or cellular immunity defects that could be addressed by implementation of prophylactic measures , such as administration of intravenous immunoglobulin ( ivig ) or proper cover with broad - spectrum antibiotics . prompt implementation of an accurate treatment is key to the final outcome in patients with sepsis . immunological monitoring could help to improve outcome in sepsis , by providing early detection of individuals at higher risk for developing complicated outcomes as well as relevant information for guiding treatment . for example , the treatment effect of ivig on mortality for patients with septic shock is currently controversial . measuring endogenous levels of immunoglobulins could improve the render of ivig in sepsis , helping the clinician to better select those patients to be treated ( those exhibiting marked hypogammaglobulinemia ) . once more , there is a dramatic absence of information on the potential role of prior endogenous immunoglobulin quantification in the clinical assays evaluating ivig for the treatment of this disease . immunological monitoring could help also to guide therapies with immunomodulatory drugs with an anti - inflammatory effect or , alternatively , with an immunostimulatory effect . although not currently practiced , monitoring of the patient 's immunological situation is feasible ( at least from a quantitative point of view ) in most hospitals . quantification of immunoglobulins , complement proteins and t cells ( cd4 , cd8 ) in peripheral blood is an easily available routine test . other tests of potential interest for immunological monitoring in sepsis include the quantification of hla - dr in the surface of blood monocytes   or the evaluation of percentages of circulating cd4cd25t - regulatory cells in blood . lastly , the use of genomic signatures ( gene expression , mirna , dna methylation profiles ) offers new opportunities to assess the immunological status of the patient . although diffuse and limited , current available information supports the development of large comprehensive studies aimed to urgently evaluate immunological monitoring as a tool to prevent or treat sepsis , and thereby to diminish the morbidity and mortality associated with this severe condition . hla : human leukocyte antigen ; ivig : intravenous immunoglobulin ; il : interleukin ; mirna : microrna . ra , jw and jfb - m provided the immunological insight and participated in writing the article . et , da - o , im - l and pr provided the clinical insight and participated in writing the article . the authors want to thank dr david livermore ( norwich medical school , university of east anglia ) for his constructive comments on this letter .
the clinical , human and economic burden associated with sepsis is huge . 
 initiatives such as the surviving sepsis campaign aim to effectively reduce risk of death from severe sepsis and septic shock . 
 nonetheless , although substantial benefits raised from the implementation of this campaign have been obtained , much work remains if we are to realise the full potential promised by this strategy . 
 a deeper understanding of the processes leading to sepsis is necessary before we can design an effective suite of interventions . 
 dysregulation of the immune response to infection is acknowledged to contribute to the pathogenesis of the disease . 
 production of both proinflammatory and immunosuppressive cytokines is observed from the very first hours following diagnosis . 
 in addition , hypogammaglobulinemia is often present in patients with septic shock . 
 moreover , levels of igg , igm and iga at diagnosis correlate directly with survival . in turn , nonsurvivors have lower levels of c4 ( a protein of the complement system ) than the survivors . 
 natural killer cell counts and function also seem to have an important role in this disease . 
 hla - dr in the surface of monocytes and counts of cd4+cd25 + t - regulatory cells in blood could also be useful biomarkers for sepsis . at the genomic level , repression of networks corresponding to major histocompatibility complex antigen presentation 
 is observed in septic shock . in consequence 
 , cumulative evidence supports the potential role of immunological monitoring to guide measures to prevent or treat sepsis in a personalised and timely manner ( early antibiotic administration , immunoglobulin replacement , immunomodulation ) . in conclusion , although diffuse and limited , current available information supports the development of large comprehensive studies aimed to urgently evaluate immunological monitoring as a tool to prevent sepsis , guide its treatment and , as a consequence , diminish the morbidity and mortality associated with this severe condition .