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The exclusive detrimental role of proinflammatory cytokines in demyelinating diseases of the CNS, such as multiple sclerosis, is controversial. Here we show that the intrathecal delivery of an HSV-1-derived vector engineered with the mouse IFN-gamma gene leads to persistent (up to 4 wk) CNS production of IFN-gamma and inhibits the course of a chronic-progressive form of experimental autoimmune encephalomyelitis (EAE) induced in C57BL/6 mice by myelin oligodendrocyte glycoprotein (MOG)(35-55). Mice treated with the IFN-gamma-containing vector before EAE onset showed an earlier onset but a milder course of the disease compared with control mice treated with the empty vector. In addition, 83% of IFN-gamma-treated mice completely recovered within 25 days post immunization, whereas control mice did not recover up to 60 days post immunization. Mice treated with the IFN-gamma-containing vector within 1 wk after EAE onset partially recovered from the disease within 25 days after vector injection, whereas control mice worsened. Recovery from EAE in mice treated with IFN-gamma was associated with a significant increase of CNS-infiltrating lymphocytes undergoing apoptosis. During the recovery phase, the mRNA level of TNFR1 was also significantly increased in CNS-infiltrating cells from IFN-gamma-treated mice compared with controls. Our results further challenge the exclusive detrimental role of IFN-gamma in the CNS during EAE/multiple sclerosis, and indicate that CNS-confined inflammation may induce protective immunological countermechanisms leading to a faster clearance of encephalitogenic T cells by apoptosis, thus restoring the immune privilege of the CNS.

Serum IL-6 levels have been shown to correlate with disease severity and prognosis in patients with plasma cell dyscrasias. Among its pleiotropic actions, IL-6 is also the major regulator of the acute phase response in humans. The possible impact on survival of the major serum acute phase proteins (s.APP) [C-reactive protein (s.CRP), alpha-1-antitrypsin (s.AAT), haptoglobin, acid alpha-1-glycoprotein and alpha-2-macroglobulin (used as control)] was assessed on a population of 103 consecutive, previously untreated myeloma patients. Univariate analysis showed that among the acute phase proteins only s.AAT (P = 0.015) and s.CRP (P = 0.027) were significantly correlated with survival. The multivariate Cox proportional hazard model applied to s.APP and other common parameters showed that s.beta-2-microglobulin (s.b2M), s.calcium, s.creatinine, BM plasma cell percentage, age and s.AAT correlated significantly with survival. Combining s.b2M and s.AAT allowed stratification of myeloma patients: those with low levels of s.b2M (< or = 3 mg/l) and of s.AAT (< or = 3 g/l) presented an excellent prognosis (median survival exceeding 10 years) while those presenting higher values of the two parameters presented a median survival of 2.5 years (P = 0.002).

A 25-year-old male drug addict presented with a rapidly progressive ascending tetraplegia, requiring assisted ventilation. One month earlier he had fever (40 degrees C) and asthenia. Cerebrospinal fluid (CSF) examination showed elevated albumin level and albuminocytologic dissociation. HIV testing was positive in both serum and CSF. Plasma exchange therapy only partially improved the symptomatology. After five months the patient remained with a moderate tetraparesis. Differences between this and other cases of Guillain-Barré syndrome in HIV-seropositive patients reported in the literature are discussed.

We used a sensitive enzyme-linked immunosorbent assay technique to measure tumor necrosis factor alpha (TNF alpha) levels in serum and cerebrospinal fluid (CSF) samples from 30 patients infected with human immunodeficiency virus type 1 and from 10 normal controls. We found detectable levels of TNF alpha in 19 of 30 CSF and in 17 of 30 serum samples. The values of TNF alpha ranged between 20-90 pg/ml. All the patients had overt AIDS. More elevated TNF alpha levels in CSF correlate with focal damage within the central nervous system (p less than 0.01). Our results suggest that an intrathecal production of TNF alpha may occur during active inflammation in course of AIDS.

Herpes simplex virus type 1 (HSV-1) IgG and IgM ELISA titers were serially determined in serum and cerebrospinal fluid (CSF) samples from 4 patients with HSV-1 encephalitis during a follow-up period of 1-26 months. In 3 out of 4 patients HSV-1 IgM titers raised in CSF during the acute phase of disease, thus allowing differentiation between primary and reactivated forms of HSV-1 encephalitis. HSV-1 IgG titers showed a sharp elevation earlier in serum than in CSF. Specific IgG index documented a large intrathecal production of HSV-1 IgG and their persistence 2 years following clinical onset. The initial trend of serum and CSF specific IgG titer represents a reliable tool for a retrospective diagnosis of HSV-1 encephalitis.

Total and virus-specific immunoglobulin (Ig) G oligoclonal bands were studied in paired serum and cerebrospinal fluid (CSF) of four patients with herpes simplex virus type 1 (HSV-1) encephalitis. We used the isoelectric focusing in agarose gel, a sensitive technique for protein separation, followed by passive transfer of proteins on nitrocellulose paper and specific immunostaining. Oligoclonal bands were observed in serum and CSF of all patients. HSV-1-specific oligoclonal IgG bands were present in the CSF only during a limited period of the disease, having their counterpart in serum during the remaining periods. Our findings contribute to tackle the issue of B-cell activation within central nervous system and peripheral blood compartments in course of HSV-1 encephalitis.

This report describes the effects of a fungal polysaccharide mixture on the Experimental Allergic Encephalitis (EAE) in guinea pigs. The clinical, histopathological and IgG intrathecal synthesis related studies in the EAE sensitized group was compared with that observed in EAE sensitized groups treated with fungal polysaccharides. The results indicate that the fungal polysaccharide mixture is capable of inducing a more localized and milder inflammatory reaction in the guinea pig with EAE. We hypothesize that the fungal polysaccharides can activate complement by the alternative pathway, subtracting it to the specific immune response to EAE.