You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
in the previous issue of critical care , herzig and colleagues   set out to determine whether blockade of the cxc chemokine receptor 3 ( cxcr3 ) attenuates inflammation and improves survival in a murine model of near lethal polymicrobial sepsis .
their results show that concomitant cxcr3 blockade and antibiotic therapy significantly improves survival when administered prior to and even shortly after sepsis .
this study is a natural extension of the authors ' prior work that demonstrates that cxcr3 blockade impedes lymphocyte trafficking , decreases systemic cytokine production and improves sepsis survival . from this body of work ,
the authors conclude that cxcr3 inhibition should be considered a potential target for anti - sepsis therapies .
although the authors ' results are compelling , the conclusion that cxcr3 signaling is detrimental in poly - microbial sepsis must be accepted with caution .
others have previously investigated the impact of cxcr3 and its ligand , cxcl10 , with strikingly dissimilar results , depending upon the model employed .
in contrast to herzig and colleagues ' report , several prior investigations have found that cxcr3 and cxcl10 were necessary for survival in adult and neonatal murine polymicrobial sepsis models .
kunkle , standiford and colleagues   in separate reports demonstrated that cxcl10 blockade worsens survival in sepsis and pneumonia .
cuenca and colleagues   showed that cxcl10 concentrations increase in the peritoneum and blood of septic neonatal mice , that cxcl10 blockade and cxcr3 blockade worsen survival , and that adjuvant augmentation of cxcl10 is protective from sepsis mortality .
in two consecutive reports , kelly - scumpia and colleagues from our laboratory implicated type i interferon production in general , and cxcl10 production specifically , as a prerequisite for hematopoietic cell function and adult mouse survival in a low - lethality polymicrobial sepsis model . in most of these latter studies ,
the lethality of the sepsis models was considerably less than used by herzig and colleagues .
the disparity between herzig and colleagues ' findings   and those of prior reports [ 3 - 7 ] may well be dependent upon the magnitude of the early inflammatory response , and should raise concern that cxcr3/cxcl10 signaling is more complex than previously suggested , and undoubtedly plays both beneficial and adverse roles in outcome to sepsis . when herzig and colleagues ' results are juxtaposed against the backdrop of known cxcr3/cxcl10 functions , and more importantly the historical landscape of failed clinical trials with inhibitors of inflammation , several questions become paramount .
what are the theoretical advantages of cxcr3/cxcl10 as a therapeutic target compared with other inflammatory targets ?
importantly , does severe murine peritoneal sepsis recapitulate human sepsis sufficiently to reasonably expect similar results in humans with severe sepsis and septic shock ? and most importantly ,
what can we learn about the mechanism of protective immunity by cxcr3/cxcl10 action ? given the ever growing complexity and reticular nature of human sepsis , is it wise to continue to pursue single therapeutic interventions for the multidimensional sepsis syndrome ? in a 21st century landscape stained by the history of failed therapeutic interdiction , the authors should be applauded for their demonstration that cxcr3 blockade begun 6 hours after the onset of sepsis is beneficial to survival . the fact that cxcr3 inhibition after the onset of sepsis improves survival gives the potential therapy a practical and broad appeal .
herzig and colleagues ' findings clearly show the detrimental side of exaggerated cxcr3 signaling in severe sepsis with high mortalities . in the clinical setting , there is little disagreement that what we call ' severe sepsis ' is presently so vaguely defined that our study populations are too heterogenous to optimize therapeutic efficacy .
although the authors demonstrate a 40% improvement in survival , the harsh fact remains that existing individual animal models are rather poor surrogates of human sepsis [ 8,10 - 12 ] .
even though the cecal ligation and puncture model is generally accepted to best replicate human peritoneal sepsis ( the ' gold standard ' to many ) , several clinical intangibles , such as pre - existing comorbidities , age , continuous fluid resuscitation , nutritional support , antibiotic therapy , and operative intervention , make human sepsis more complex , and routinely difficult to replicate in mice .
juxtaposed with the murine versus human sepsis conundrum stands the mortality disparity between the authors ' cecal ligation and puncture model , which was 90% across the board and 50% in the group that showed a benefit , compared to an overall mortality of approximately 25% in human sepsis . compared to other , older anti - inflammatory therapeutic targets ,
cxcr3 is a relative new - comer with only a handful of studies dealing with its role in polymicrobial sepsis .
more detailed investigations are warranted to better understand the receptor 's scope of action and full therapeutic potential . in their prior report
, herzig and colleagues partially addressed this issue by implicating cxcr3 blockade in reducing peritoneal lymphocyte recruitment and interleukin-6 and macrophage inflammatory protein 2 production .
however , given the multitude of cellular responses and inflammatory mediators that orchestrate the sepsis syndrome , more detailed investigations are required before we will truly understand the mechanism of cxcr3 blockade and its therapeutic potential
. however , herzig and colleagues are to be congratulated on advancing the field , and drawing attention to the important role that individual chemokines play in sepsis survival .
mjd was supported by a training grant in burn and trauma research ( t32 gm-08431 ) awarded by the national institute of general medical sciences , usphs .
blockade of the cxc chemokine receptor 3 ( cxcr3 ) attenuates inflammation and improves survival in a murine model of near lethal polymicrobial sepsis . 
 however , given the multitude of cellular responses and inflammatory mediators that orchestrate sepsis syndrome , more detailed investigations will be required before a complete understanding of the mechanism(s ) of cxcr3 blockade and its therapeutic potential are revealed .