Tumor necrosis factor alpha (TNFα) and neurological diseases Failure in detecting TNFα in the cerebrospinal fluid from patients with multiple sclerosis, AIDS dementia complex, and brain tumours

Gallo, Paolo; Piccinno, Maria Grazia; Kržalić, Lj.; Tavolato, B.

doi:10.1016/0165-5728(89)90071-4

Cited by 72 publications

(10 citation statements)

References 21 publications

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“…Consistent with the low TNF immunoreactivity in PBMC, are reports of undetectable levels of TNF in serum and CSF from patients with MS, regardless ofthe extent ofclinical activity (7,8). However, two studies have reported increased production of TNF by macrophages isolated from peripheral blood and cerebrospinal fluid of MS patients after activation with lipopolysaccharide and phorbol myristate acetate (9), or concanavalin A and phytohemagglutinin (10).…”

Section: Discussionmentioning

confidence: 82%

Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions.

Selmaj

Raine

Cannella³

et al. 1991

J. Clin. Invest.

707

292

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Multiple sclerosis (MS) brain tissue, spleen, and PBMC were studied using immunocytochemistry and FACS® for immunoreactivity for lymphotoxin (LT) and TNF. Both cytokines were identified in acute and chronic active MS lesions but were absent from chronic silent lesions. LT was associated with CD3+ lymphocytes and Leu-M5+ microglia cells at the lesion edge and to a lesser extent, in adjacent white matter. TNF was associated with astrocytes in all areas of the lesion, and with foamy macrophages in the center of the active lesion. In acute lesions, immunoreactivity for TNF in endothelial cells was noted at the lesion edge. No LT or TNF reactivity was detected in Alzheimer's or Parkinson's disease brain tissues but was present at lower levels in central nervous system (CNS) tissue from other inflammatory conditions, except for adrenoleucodystrophy which displayed high levels of LT in microglia. No increase in LT and TNF reactivity was detected in spleen and PBMC of MS patients suggesting specific reactivity within the CNS. These results indicate that LT and TNF may be involved in the immunopathogenesis of MS, and can be detected in both inflammatory cells and cells endogenous to the CNS. (J. Clin. Invest. 1991. 87:949-954.)

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Section: Discussionmentioning

confidence: 82%

Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions.

Selmaj

Raine

Cannella³

et al. 1991

J. Clin. Invest.

707

292

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“…Some groups have reported elevated CSF TNF-a levels correlating with MS severity (Hauser et al, 1990;Sharief and Hentges, 1991;Tsukada et al, 1991), whereas others failed to detect correlations (Maimone et al, 1991) or even TNF-a in MS CSF (Franciota et al, 1989;Gallo et al, 1989;Peter et al, 1991;Noseworthy et al, 1993), probably depending on some of the methodological difficulties discussed above. els of LT mRNA in MS exacerbations (Rieckmann et al, 1994(Rieckmann et al, , 1995.…”

Section: Proinflammatory Cytokines In Msmentioning

confidence: 88%

Review: cytokines and the pathogenesis of multiple sclerosis

1996

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“…For example, the observed decrease of the 3-adrenergic control of TNF-a production may lead to an excessive extracellular level ofthis cytokine, which was recently found to be elevated in plasma (23), cerebrospinal fluid (24) (however, see ref. 25), and microglia (26) of AIDS patients with neurological involvement. TNF-a has been shown to be toxic for oligodendrocytes and myelin (27), to induce major histocompatibility complex antigen expression in astrocytes (12,28), to stimulate the astroglial expression and production of interleukin 6 (29,30) and ofcolony-stimulating factors (30,31), to stimulate astrocyte proliferation (32), to synergize with other inflammatory cytokines such as interferon y (12), to facilitate the passage of T cells across the blood-brain barrier (33), and to stimulate HIV replication in infected cells (see ref.…”

Section: Methodsmentioning

confidence: 99%

Human immunodeficiency virus coat protein gp120 inhibits the beta-adrenergic regulation of astroglial and microglial functions.

Levi

Patrizio

Bernardo

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

141

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The goal of our study was to assess whether the human immunodeficiency virus (HIV) coat protein gpl20 induces functional alterations in astrocytes and microglia, known for their reactivity and involvement in most types of brain pathology. We hypothesized that gpl20-induced anomalies in glial functions, ifpresent, might be mediated by changes in the levels of intracellular messengers important for signal transduction, such as cAMP. Acute (10 min) exposure of cultured rat cortical astrocytes or microglia to 100 pM gpl20 caused only a modest (50-60%), though statistically significant, elevation in cAMP levels, which was antagonized by the (3-adrenergic receptor antagonist propranolol. More importantly, the protein substantially depressed [by 30% (astrocytes) and 50% (microglia)] the large increase in cAMP induced by the .3-adrenergic agonist isoproterenol (10 nM), without affecting that induced by direct adenylate cyclase stimulation by forskolin. Qualitatively similar results were obtained using a glial fibrillary acidic protein (GFAP)-positive human glioma cell line. The depression of the (3-adrenergic response had functional consequences in both astrocytes and microglia. In astrocytes we studied the phosphorylation of the two major cytoskeletal proteins, vimentin and GFAP, which is normally stimulated by isoproterenol, and found that gpl20 partially (40-50%) prevented such stimulation. In microglial cells, which are the major producers of inflammatory cytokines within the brain, gpl20 partially antagonized the negative ,3-adrenergic modulation of lipopolysaccharide (10 ng/ml)-induced production of tumor necrosis factor a. Our results suggest that, by interfering with the ,B-adrenergic regulation of astrocytes and microglia, gpl20 may alter astroglial "reactivity" and upset the delicate cytokine network responsible for the defense against viral and opportunistic infections.The pathogenesis of AIDS encephalopathy, a complication present in 50-80% of AIDS patients, is still largely unknown (1-4). Besides direct infection of brain cells by human immunodeficiency virus (HIV), which seems to occur mainly in microglia (2-6), the intrinsic brain macrophages, other factors could contribute to the development of brain damage, such as neurotoxic substances produced by brain cells and/or by invading hematic cells, or proteins encoded by the viral genome. Among the latter, the envelope glycoprotein gp120 was reported to cause neuronal death in cell cultures from the rodent central nervous system (reviewed in ref. 7; see also ref. 8) and to induce interleukin 1 (9) and to cause learning impairment (10) in the rat brain in vivo. In the present study we evaluated the possibility that the viral protein may cause functional alterations in glial cell types (astrocytes and microglia) known for their reactivity and involvement in most neurological diseases. We found that acute exposure to picomolar gp120 depressed the (3adrenergic agonist-induced formation of cAMP and altered important cAMP-regulated functions in both cel...

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Tumor necrosis factor alpha (TNFα) and neurological diseases Failure in detecting TNFα in the cerebrospinal fluid from patients with multiple sclerosis, AIDS dementia complex, and brain tumours

Cited by 72 publications

References 21 publications

Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions.

Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions.

Review: cytokines and the pathogenesis of multiple sclerosis

Human immunodeficiency virus coat protein gp120 inhibits the beta-adrenergic regulation of astroglial and microglial functions.

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