The study was conducted with 84 healthy, nonsmoking men. They were split into placebo and single injection of rhIL-10 groups (the "rh" stands for recombinant human). There was a huge range in dosages, from 0.1 microgram/kg body weight up to 100.0 microgram/kg body weight. Each subject received their injection for 30 seconds through IV.
Subjects had mild-to-moderate flu like symptoms (fever, chills, myalgia, cough, nasal congestion...), but "no clinically significant adverse effects on clinical chemistry, serology, or urinalysis were observed. (Huhn et al 700)" Obviously, IL-10 levels increased. There were increased numbers of neutrophils and monocytes. There was a decrease in lymphocyte numbers.
I think it would be really interesting to see a study with IL-10 administered before a MCAO is induced, and to see if IL-10 can actually be used as a preventative measure. From the papers we've read over the past two weeks, I would guess that IV IL-1o treatment pre-stroke would decrease lesion volume and would improve behavior scores. Would IV IL-1o treatment help post-stroke? I wonder...
References:
Vila et al. "Levels of Anti-Inflammatory Cytokines and Neurological Worsening in Acute Ischemic Stroke." Stroke (2003): 671-675. Web. 22 Feb 2011.
Huhn et al . "Pharmacokinetics and Immunomodulatory Properties of Intravenously Administered Recombinant Human Interleukin-l0 in Healthy Volunteers." Blood 87.2 (1996): 699-705. Web. 2 Mar 2011. .
Sorry, there was supposed to be a link to the Pharmacokinetics paper at the end its citation!
ReplyDeleteHere it is:
http://bloodjournal.hematologylibrary.org/cgi/reprint/87/2/699.pdf
Considering the Huhn et al. paper is from 1996, I suppose the findings are very exciting, but I would have liked to see more recent and more convincing work on administration of IL-10 as a preventative measure. Figures 2 and 3 of the Huhn paper are particularly unsatisfying for me, because it seems like there is no pattern related to the dosage differences, the bars are just all over the place. I'm sure part of this comes from having only 6 men in each test group, which is understandable for a first-of-its-kind study, but I would have liked for the Vila et al. paper to have substantiated its claim that IL-10 could be given as a preventative measure with a stronger citation. The short-term nature of the effects of IV IL-10 administration demonstrated by Figure 2 of the Huhn paper do not strike me as particularly convincing for Vila's assertion, "those subjects genetically predisposed might be treated with exogenous IL-10 to prevent stroke" (674).
ReplyDeleteHowever, I think Vila is justified in saying IL-10 administration could prevent clinical worsening in acute stroke based on the Huhn study. Reduced lymphocytes seems like a good thing for a recent stroke victim, but do we want them to have such elevated neutrophils and monocytes? I don't remember ever talking in class about the different roles of different cells in response to stroke, so if someone could enlighten me that would be great.
The reduction of cytokines seems more promising to me (Figure 3), but I would be concerned about the potential rebound the body would make after the initial effects of IV IL-10 wore off. Would increased production of TNF-alpha at 24 and 48 hours offset the benefits of reduced TNF-alpha at 2 and 12 hours?
I think studying IL-10 administration in conjunction with an MCAO in mice would tell us a lot, but I would prefer to administer the IL-10 after the MCAO to evaluate how much it might prevent clinical worsening if a patient came in shortly after a stroke.