There is a balance between pro- and anti-inflammatory cytokines in a normal physiological state. This balance is lost after stroke.[20
] In this study, we evaluated the course of inflammatory cytokines in AIS patients and compared its level with ITIH4 and outcome of AIS patients to identify potential candidate cytokines for the prediction of clinical outcome in AIS patients.
Out of the 12 cytokines, we observed that only six cytokines were in the measurable range of the kit (10 pg/mL), which included four pro-inflammatory cytokines (i.e., IL-1B, IL-2, IL-8 and TNF-α) and two anti-inflammatory cytokines (IL-10 and IL-6).
We observed a decrease in the serum level of ITIH4 after AIS, which further increased with the improvement of patients. Decrease in ITIH4 level correlates with CT scan infarct volume. Results of the current study are consistent with our earlier reports.[18
IL-8 is predominantly produced within the central nervous system by damage of tissue at the site of ischemia. IL-8 mRNA was also reported to increase in peripheral blood mononuclear cell (PBMC) after stroke. The plasma level of IL-8 (chemokines, CXCL8) increased after stroke and remained elevated up to 1 month.[21
] IL-1b and IL-17 were also elevate systemically after AIS.[22
] IL-1b and IL-17 induced the secretion of IL-8.[23
] We also observed a high IL-8 level in the serum of AIS patients throughout the follow-up. Thus, our results are in agreement with the earlier report. But, interestingly, in contrast to previous reports, we did not observe IL-17 in a detectable level, while IL-1B was found to be elevated only at 24 h and 144 h. This shows that IL-8 might be regulated by other mechanisms also. A recent study by Asare et al
. showed that decrease in IL-1b increases the risk of stroke, and a mild increase in IL-1b is protective against stroke.[25
] Thus, the observed increase in IL-1b at 24 h and 144 h in AIS patients may be due to protective immune response after AIS.
IL-10 is known to be the main down-regulator of the deleterious effect of pro-inflammatory cytokines.[26
] IL-10 was reported to be significantly decreased after stroke as compared with the control, and again increased at the seventh day after stroke, and was associated with neurological deficit and/or stroke outcome.[9
] We also observed a decrease in serum IL-10 levels after AIS, which further increased after 72 h with improvement of the AIS patient, and also correlated with ITIH4.
IL-6 and TNF-α have been reported to increase after stroke.[28
] An increase in serum IL-6 and TNF-α within 24 h after AIS was also observed in the current study. The TNF-α level further decreased with an improvement in the AIS patients. IL-6 is a pleiotropic cytokine and can function as a pro-inflammatory cytokine by enhancing leukocyte recruitment by up-regulating production of chemokines and adhesion molecule expression.[29
] IL-6 also serves as an anti-inflammatory cytokine by inhibiting TNF-α expression and inducing the expression of soluble TNF-α receptors and the IL-1R antagonist.[31
] Similarly, a recent report by Al-Bahrani et al
. demonstrates that the TNF-α level was also found to decrease in response to anti-platelet therapy.[33
] Therefore, decrease in the TNF-α after 48 h in the follow-up sample of AIS patients might be due to the anti-inflammatory effect of IL-10, reported anti-inflammatory activity of IL-6 or as a result of anti-platelet therapy, as treatment regiments for AIS also include the anti-platelet drug. These could be the possible explanation for further decrease in TNF-α in AIS patients after 48 h.
In an earlier study, it was shown that the IL-2 level decreases with the increase in anti-inflammatory cytokine IL-10.[17
] Results of the current study also show that IL-2 decreases after increase in the anti-inflammatory response. Pro-inflammatory cytokines IL-1A, IL-12, IL-17A, INF-y, GM-CSF and anti-inflammatory cytokine IL-4 were not detected in the serum samples. This shows that, possibly, there may be less involvement of these cytokines in poststroke inflammatory reaction.