Human CD14 blocking peptide

Background:Granulocytes and monocytes are the first cells to invade the brain post stroke and are also being discussed as important cells in early neuroinflammation after seizures. We aimed at understanding disease specific and common pathways of brain-immune-endocrine-interactions and compared immune alterations induced by stroke and seizures. Therefore, we compared granulocytic and monocytic subtypes between diseases and investigated inflammatory mediators. We additionally investigated if seizure type determines immunologic alterations. Material and Methods:We included 31 patients with acute seizures, 17 with acute stroke and two control cohorts. Immune cells were characterized by flow cytometry from blood samples obtained on admission to the hospital and the following morning. (i) Monocytes subpopulations were defined as classical (CD14(++)CD16(-)), (ii) intermediate (CD14(++)CD16(+)), and (iii) non-classical monocytes (CD14(dim)CD16(+)), while granulocyte subsets were characterized as (i) "classical granulocytes" (CD16(++)CD62L(+)), (ii) pro-inflammatory (CD16(dim)CD62L(+)), and (iii) anti-inflammatory granulocytes (CD16(++)CD62L(-)). Stroke patient's blood was additionally drawn on days 3 and 5. Cerebrospinal fluid mitochondrial DNA was quantified by real-time PCR. Plasma High-Mobility-Group-Protein-B1, metanephrine, and normetanephrine were measured by ELISA. Results:HLA-DR expression on monocytes and their subpopulations (classical, intermediate, and non-classical monocytes) was reduced after stroke or seizures. Expression of CD32 was increased on monocytes and subtypes in epilepsy patients, partly similar to stroke. CD32 and CD11b regulation on granulocytes and subpopulations (classical, anti-inflammatory, pro-inflammatory granulocytes) was more pronounced after stroke compared to seizures. On admission, normetanephrine was upregulated in seizures, arguing for the sympathetic nervous system as inducer of immune alterations similar to stroke. Compared to partial seizures, immunologic changes were more pronounced in generalized tonic-clonic seizures. Conclusion:Seizures lead to immune alterations within the immediate postictal period similar but not identical to stroke. The type of seizures determines the extent of immune alterations.

Background: Complete recovery of the CD4 T cell count is uncommon among chronically HIV-infected individuals with very low pre-treatment CD4 count. We studied the prevalence of chronically immune recovery and its associated factors including immune characteristics chronic HIV-infected Thais. Methods: Treatment-naive participants (n = 375) from the HIV-NAT 006 cohort with a pre-treatment CD4 T cell count after initiating antiretroviral therapy (ART) and having achieved a suppressed viremia (HIV-RNA level < 400 copies/mL) were retrospectively followed at the Thai Red Cross AIDS Research Centre, Bangkok, Thailand. Suboptimal immune recovery (SIR) was defined as having a CD4thorn T cell count <200 cells/mm(3) for 3 years after ART initiation. A case-control sub-study matched for age, sex and pre-ART CD4 T cell count was conducted to compare immunological characteristics between SIR (n = 17) and non-SIR (n = 24) participants. Immunological biomarkers such as interleukin-7 (IL-7) and soluble CD14 (sCD14) and other covariates including cytomegalovirus (CMV) DNA level, baseline hemoglobin level, hepatitis B and C co-infections, and T cell subsets associated with immune activation and exhaustion were evaluated. Results: Among 375 participants with pre-ART CD4 T cell counts < 200 cells/mm(3), the prevalence of SIR was 39.7%, 19.7% and 7.7% at years 1, 2 and 3 after starting ART, respectively. In a multivariate analysis, a pre-ART CD4 T cell count <= 100 cells/mm(3) (adjusted odds ratio [aOR] 9.45, 95% CI 2.92-30.61, p < 0.001), older age (aOR 1.07, 95% CI 1.01-1.13, p = 0.029) and baseline HIV-RNA level (aOR 0.36, 95% CI 0.21-0.59, p < 0.001) were independently associated with SIR at year 3 after ART initiation. In the matched case-control sub-study (cases = 17, controls = 24), there was a higher prevalence of hepatitis C co-infection (18.8% vs. 0%, p = 0.05), lower sCD14 levels (mean, 6.23 vs. 6.27 log(10) pg/mL, p = 0.04), lower CD8 T cell counts (mean, 514 vs. 876, p = 0.0003), lower CD4/CD8 T cell ratio (mean, 0.27 vs. 0.41, p = 0.01) and higher expression of PD1 on CD8(+) T cells (74.2% vs. 65.1%, p = 0.02) observed in SIR participants compared to their non-SIR counterparts at year 3 after ART initiation. Conclusions: Nearly 10% of the study participants who had achieved virological suppression failed to recover a CD4 T cell count > 200 cells/mm(3) after 3 years of ART which was with a very low pre-ART CD4 T cell count and older age. The long-term clinical outcomes of SIR participants need to be further explored.