Gamma interferon is spontaneously released by alveolar macrophages and lung T lymphocytes in patients with pulmonary sarcoidosis.

Robinson, Bruce; McLemore, Theodore L.; Crystal, Ronald G.

doi:10.1172/jci111852

Cited by 417 publications

(253 citation statements)

References 50 publications

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“…In sarcoidosis, IFN-, TNF-and IL-1 have been reported to be increased in BALF cells and granulomatous lymph nodes in patients with sarcoidosis [4][5][6][7]. Prior & Haslam [32] showed elevated IFN-concentrations in sera of patients with pulmonary sarcoidosis.…”

Section: Discussionmentioning

confidence: 99%

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Circulating soluble intercellular adhesion molecule-1 (sICAM-1) in patients with sarcoidosis

Shijubo

Imai

Shigehara³

et al. 1996

Clinical and Experimental Immunology

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sICAM‐1 has been elevated in sera of specific inflammatory diseases, and circulating sICAM‐1 concentrations reflect disease activity in these diseases. We measured circulating sICAM‐1 concentrations and serum angiotensin‐converting enzyme (SACE) activity in patients with sarcoidosis. Patients with sarcoidosis had significantly increased circulating sICAM‐1 concentrations (62.8±33.5U/ml) and SACE activity (23.7±7.4U/l) compared with controls (circulating sICAM‐1 50.9±12.1U/ml, and SACE 13.5±3.8U/l). Successive measurements showed that circulating sICAM‐1 values changed in parallel with disease activity in sarcoidosis. In the progressive disease group (progressed or without change for 2 years or more), circulating sICAM‐1 values (102.2±35.3U/ml) at the time of diagnosis were significantly increased compared with those in the regressive disease group (disappeared or regressed within 2 years) (46.4±12.6U/ml). However, there was no significant difference in SACE activity of the regressive and progressive disease groups. Fifteen patients with a high value of circulating sICAM‐1 (>75U/ml, mean of controls+2s.d.) all had progressive disease, while only 15 of 44 patients with a high value of SACE had progressive disease. Circulating sICAM‐1 will be a useful blood marker to predict outcome and to monitor disease activity in sarcoidosis.

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Section: Discussionmentioning

confidence: 99%

“…Excess synthesis of proinflammatory cytokines such as IL-1 , tumour necrosis factor-alpha (TNF-) and interferon-gamma (IFN-) has been found in bronchoalveolar lavage fluid (BALF) cells and granulomatous lymph nodes of patients with sarcoidosis [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Circulating soluble intercellular adhesion molecule-1 (sICAM-1) in patients with sarcoidosis

Shijubo

Imai

Shigehara³

et al. 1996

Clinical and Experimental Immunology

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“…Total RNA of 5 ϫ 10 6 cultured BAL fluid cells was isolated using Isogen (Nippon Gene, Toyama, Japan) and quantified by measurement of absorbance at 260 nm. To synthesize cDNA, 1 g of total RNA was incubated in the presence of Moloney murine leukemia virus reverse transcriptase (Life Technologies, Gaithersburg, MD) and 5 ng/ml oligo(dT) [12][13][14][15][16][17][18] primers (Pharmacia Biotech, Uppsala, Sweden) for 30 min at 42°C using reaction conditions described by the manufacturer (Life Technologies), and samples were stored at Ϫ80°C.…”

Section: Analysis Of Cytokine Gene Expressionmentioning

confidence: 99%

“…Many cytokines and chemokines play an important role during the processes of sarcoid granuloma (17). On the basis of recent Th1 and Th2 paradigms, the cytokine profile of sarcoidosis is Th1 dominant when disease activity is high (17)(18)(19). Recent studies have demonstrated enhanced expression of IL-12 (20 -22) and IL-12R (23,24) in sarcoid lungs.…”

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confidence: 99%

IL-12 and IL-18 Are Increased and Stimulate IFN-γ Production in Sarcoid Lungs

Shigehara

Shijubo²,

Ohmichi

et al. 2001

The Journal of Immunology

167

101

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Sarcoidosis is a systemic chronic granulomatous disease of unknown cause. Recent investigations revealed that the cytokine profile in inflamed lesions of sarcoidosis is Th1 dominant. To obtain better immunopathologic understanding of sarcoidosis, we examined the expression of IL-12 and IL-18 and their roles in IFN-γ production in pulmonary sarcoidosis. Sarcoid cases had significantly elevated levels of IL-12 (p40 and p70) and IL-18 in bronchoalveolar lavage (BAL) fluids compared with healthy subjects. IL-12 p70 and IL-18 were immunohistochemically expressed in the epithelioid cells and giant cells of sarcoid granulomas. Significant induction of IFN-γ, IL-12 p70, and IL-18 was observed from sarcoid BAL fluid cells with LPS stimulation, whereas LPS tended to induce only IL-12 p70 in BAL fluid cells from healthy subjects. Sarcoid cases had significantly greater IFN-γ induction with LPS stimulation than healthy subjects did. IL-18 mRNA expression was observed in freshly isolated sarcoid BAL fluid cells as well as in LPS-stimulated sarcoid BAL fluid cells, but IFN-γ and IL-12 mRNA expression was observed only in LPS-stimulated BAL fluid cells. Treatment with anti-IL-12- and anti-IL-18-neutralizing Abs significantly inhibited IFN-γ production from LPS-stimulated BAL fluid cells of sarcoid cases. Coadministration of rIL-12 or rIL-18 induced greater IFN-γ production in sarcoid BAL fluid cells than in normal BAL fluid cells. We concluded that bioactive IL-12 and IL-18 were produced in sarcoid BAL fluid cells and synergistically induced IFN-γ production, indicating important cytokines in the Th1 response of sarcoidosis.

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“…In order to understand this supposed mechanism in sarcoidosis, we therefore focused our work on critical cell surface receptors which bind exogenous stimuli [2][3][4]. It is well established that immunity-related receptors and proinflammatory cytokines, which include tumour necrosis factor (TNF)-α [5], interleukin (IL)-1 β [6], IL-2 [7], IL-6, IL-8 [8] and interferon (IFN)-γ [9], play a pivotal role in the formation of granulomas in sarcoidosis. The early phase in developing sarcoid granulomas is characterized by the accumulation and activation of T helper cells type 1 (Th1) lymphocytes, which lead to an immune response.…”

Section: Introductionmentioning

confidence: 99%

Toll-like receptor (TLR) 4 polymorphisms are associated with a chronic course of sarcoidosis

Pabst

Baumgarten

Stremmel

et al. 2006

Clinical and Experimental Immunology

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SummaryThe aetiology of sarcoidosis, an inflammatory granulomatous multi-system disorder, is unclear. It is thought to be the product of an unknown exogenous antigenic stimulus and an endogenous genetic susceptibility. Toll-like receptors (TLR) are signal molecules essential for the cellular response to bacterial cell wall components. Lipopolysaccharide (LPS), for example, binds to TLR 4. Two different polymorphisms for the TLR4 gene (Asp299Gly and Thr399Ile) have been described recently. This leads to a change in the extracellular matrix function of TLR4 and to impaired LPS signal transduction. We genotyped a total of 141 Caucasian patients with sarcoidosis and 141 healthy unrelated controls for the Asp299Gly and Thr399Ile polymorphisms in the TLR4 gene. The mutations were identified with polymerase chain reaction followed by restriction fragment length polymorphism (RFLP) analysis. Among sarcoidosis patients the prevalence for each Asp299Gly and Thr399Ile mutant allele was 15·6% (22/141). In the control group the prevalence was 5·67% (8/141) ( P = = = = 0·07). In the subgroup of patients with acute sarcoidosis there was no difference in the control group ( P = = = = 0·93), but there was a highly significant association between patients with a chronic course of sarcoidosis and TLR4 gene polymorphisms ( P = = = = 0·01).

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Gamma interferon is spontaneously released by alveolar macrophages and lung T lymphocytes in patients with pulmonary sarcoidosis.

Abstract: Abstractosis may, at least in part, be due to suppression of IFN-y release.

Cited by 417 publications

References 50 publications

Circulating soluble intercellular adhesion molecule-1 (sICAM-1) in patients with sarcoidosis

Circulating soluble intercellular adhesion molecule-1 (sICAM-1) in patients with sarcoidosis

IL-12 and IL-18 Are Increased and Stimulate IFN-γ Production in Sarcoid Lungs

Toll-like receptor (TLR) 4 polymorphisms are associated with a chronic course of sarcoidosis

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