ABSTRACT
The tachykinin neuropeptide substance P (SP) has an important signaling role in both the nervous and the immune systems. Two naturally occurring variants of the neurokinin-1 receptor (NK1R) mediate the effects of SP, full-length receptor (NK1R-F) and a truncated form (NK1R-T) that lacks 96 amino acid residues at the C-terminus. We previously reported decreased expression of the NK1R-F in the CNS of HIV-positive individuals in comparison to HIV-negative control subjects. There were no differences in the expression of the NK1R-T in the same groups. In the current study, we quantified the expressions of SP precursor mRNA preprotachykinin (TAC1), NK1R (full and truncated forms), viral load (HIV-gag) and several proinflammatory and immune markers (CD4, CCR5, CXCR4, fractalkine, IL-6, IL-10, CCL2, CCL20 and CD163) in the frontal cortex of autopsied brains from HIV-1-positive individuals with or without HIV-associated neuropathology. The expressions of SP and, to lesser extent, NK1R-F were decreased while the expressions of CXCR4, CCR5 and CCL2 were increased in CNS of individuals with HIV-associated neuropathology. There was no change in HIV loads associated with neuropathology; however, we found a positive correlation between viral loads and the expression of haptoglobin-hemoglobin scavenger receptor CD163. An analysis of CSF from corresponding samples demonstrated an increase in proinflammatory markers (CCL2 MIP-1α and MIP-1ß) associated with neuropathology. Although our data confirm the overall inflammatory nature of HIV-associated neuropathology, we observed a decrease in the expression of SP and NK1R-F, which is also associated with other forms of neuroinflammation.
Subject(s)
AIDS-Associated Nephropathy/genetics , AIDS-Associated Nephropathy/immunology , Frontal Lobe/immunology , Frontal Lobe/metabolism , Gene Expression Regulation , Receptors, Neurokinin-1/biosynthesis , Substance P/biosynthesis , AIDS-Associated Nephropathy/cerebrospinal fluid , AIDS-Associated Nephropathy/pathology , Adult , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Biomarkers/cerebrospinal fluid , Biomarkers/metabolism , Female , Frontal Lobe/pathology , Gene Expression Profiling , Humans , Male , Middle Aged , Receptors, Cell Surface/metabolism , Viral LoadABSTRACT
A 32-year-old homosexual man was admitted because of acute headache, fever, and lymphoadenopathy. The neurological examination revealed nuchal rigidity and positive Kernig's sign. The cell count of cerebrospinal fluid (CSF) at the time of admission, however, was four per microliter and subsequently increased up to 31 per microliter in three days. The serum antibody for human immunodeficiency virus (HIV) was positive in ELISA and the cell number of CD4 positive population decreased to 280. The RT-PCR for HIV RNA was 7.6 x 10(5) copies per milliliter, which gradually decreased, leading to the diagnosis of meningitis due to HIV itself. The Western blotting for HIV antibodies were positive for p24, p40 and p55, whereas that for gp 41 was negative in serum and CSF, suggesting that the meningitis occurred during the seroconversion in this patient. We surmise that aseptic meningitis during HIV primary infection usually results in mild CSF pleocytosis and sometimes leads to even normocytosis shown as in this patient, probably because cellular immunity is temporally suppressed in acute HIV infection.
