Japan. SinarySerum interleukin 6 (IL-6) levels were measured in 75 patients with lung cancer and in 20 patients with benign lung diseases. IL-6 was detectable in 29 patients with lung cancer (39%), but was not detectable in any of the patients with benign lung diseases. Serum C-reactive protein levels and plasma fibrinogen levels were significantly higher and serum albumin concentration was significantly lower in lung cancer patients with detectable serum IL-6 levels than in those without detectable serum IL-6 levels and in patients with benign lung diseases. On the other hand, no significant difference was observed in blood platelet counts in these three groups. Moreover, serum IL-6 levels were not significantly different in lung cancer patients with or without clinically demonstrated distant metastasis. These results suggest that IL-6 may be a mediator of various reactions including an inflammatory response in lung cancer patients.Keywords interleukin 6; lung cancer; C-reactive protein; fibrinogen; cachexia; inflammatory response Interleukin 6 (IL-6) is known as a multifunctional cytokine which plays a central role in the host defence mechanism by regulating immune responses, haematopoiesis and acutephase reactions (Kishimoto, 1989). Recently, much attention has been focused on its role in the pathogenesis and progression of various malignancies. It has been reported that IL-6 is an autocrine growth factor for renal cell carcinoma cells (Miki et al., 1989;Koo et al., 1992) and that IL-6 is produced by other non-haematopoietic tumour cells, including bladder carcinoma (Rawle et al., 1989), ovarian carcinoma (Watson et al., 1990) and glioblastoma (Meir et al., 1990). In animal systems, IL-6 appears to have an important role in mediating cancer cachexia (Strassmann et al., 1992). Moreover, elevation of the serum IL-6 level is an adverse prognositic factor in patients with metastatic renal cell carcinoma (Blay et al., 1992). However, there is still little information about the role of IL-6 in vivo in patients with various malignancies.In patients with lung cancer, we have already reported that malignant pleural effusions contain IL-6 (Yanagawa et al., 1992), and we (Mizuno et al., 1994) and others (Matsuguchi et al., 1991) have reported that several lung cancer cell lines constitutively produce IL-6 in vitro. To clarify further the role of IL-6, we examined serum levels of IL-6 in patients with lung cancer. The relationship between serum IL-6 levels and the characteristics of the patients was also analysed. Enzyme immunoassay of IL-6 Serum levels of IL-6 were assayed essentially as described previously (Yanagawa et al., 1992). In brief, microtitre plates (Nunc, Naperville, IL, USA) were coated with anti-IL-6 monoclonal antibody in 100 per well phosphate-buffered saline (PBS). After overnight incubation at 4°C, the wells were blocked with 0.1% bovine serum albumin (BSA) in PBS and washed three times. Volumes of 200 MI of test samples were added to the duplicate wells. The plates were incubated at 37C for 24 h. Aft...

The presence of vascular endothelial growth factor (VEGF) was examined by enzyme immunoassay in 60 cytology-documented malignant pleural effusions associated with primary lung cancer and 51 other benign and malignant pleural effusions. Exudative pleural effusions contained significantly higher amounts of VEGF than transudative pleural effusions. Among exudative pleural effusions, levels of VEGF in malignant pleural effusions associated with lung cancer were significantly higher than those of benign exudative pleural effusions. There was no significant difference in pleural VEGF in patients with different histological types or clinical stages of lung cancer. Serial measurement of pleural VEGF levels was performed in six lung cancer patients treated with intrapleural instillation of recombinant interferon gamma, and reduction of pleural effusion was associated with decreasing pleural VEGF levels. These findings suggest that VEGF has a role in the accumulation of exudative pleural effusions, especially that of malignant pleural effusion associated with lung cancer.

Background: Nuclear factor (NF)-κB is a transcription factor known to regulate allergy-associated cytokine and chemokine production related to the induction of inflammation. IκB kinase β (IKKβ), which is responsible for activation of the NF-κB pathway, may be an ideal molecular target to inhibit this process. IMD-0354 [N-(3,5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide] is an attractive novel IKKβ inhibitor that prevents the production of inflammatory cytokines in various diseases, although it is not known if IMD-0354 is effective against allergic inflammation. This study aimed to elucidate the antiallergic effects of a newly synthesized IKKβ inhibitor, IMD-0354, in a mouse model of allergic inflammation. Methods: We generated ovalbumin (OVA)-sensitized mice which were then challenged with OVA. IMD-0354 was administered intraperitoneally to therapeutic groups. Lung histopathology and the concentrations of cytokines and chemokines in bronchoalveolar lavage fluid (BALF) and supernatants of lung homogenates were determined. Results: Administration of IMD-0354 ameliorated airway hyperresponsiveness and reduced the numbers of bronchial eosinophils and mucus-producing cells in OVA-sensitized mice. The total numbers of cells and eosinophils in BALF were also reduced by treatment with IMD-0354. Treatment with IMD-0354 inhibited the production of Th2 cytokines such as interleukin (IL)-5 and IL-13 and eotaxin in the airways and/or lungs of OVA-sensitized mice, but it did not affect the restoration of Th1 cytokines such as IL-12 and interferon-γ under the same experimental conditions. IgE production was also inhibited by IMD-0354. Conclusion: A specific IKKβ inhibitor, IMD-0354, improved allergic airway inflammation and hyperresponsiveness in mice. IMD-0354 may have therapeutic potential for bronchial asthma.

An IgE-dependent histamine-releasing factor (HRF p23; also known as translationally controlled tumor protein or p23) stimulates the release of histamine, IL-4, and IL-13 from a subpopulation of highly allergic donor basophils. It has also been shown to act as a chemoattractant for eosinophils. To elucidate novel functions of HRF p23 in airway inflammation, we examined the effects of human recombinant HRF p23 (hrHRF) on bronchial epithelium and found that hrHRF stimulated the secretions of IL-8 and granulocyte/macrophage colony-stimulating factor by both primary cultures of human bronchial epithelial cells and BEAS-2B cells. In response to hrHRF, these cells induced IL-8 mRNA expression within 4 h. H2O2, but not IL-1 beta or tumor necrosis factor-alpha, stimulated secretion of HRF p23 by BEAS-2B cells, suggesting that oxidative stress may trigger the release of HRF p23 from bronchial epithelial cells. Bronchoalveolar lavage (BAL) from healthy volunteers contained only trivial or undetectable amounts of HRF p23. Significantly higher amounts of HRF p23 were recovered from BAL fluid taken from asthmatic patients, and the amounts of HRF p23 were further elevated in patients with idiopathic eosinophilic pneumonia. Our results demonstrate for the first time that HRF p23 can stimulate nonimmune epithelium. HRF p23 derived from bronchial epithelial cells may regulate complex cytokine networks in eosinophil-dependent inflammation of the human airway.

Many lung cancer patients have coexisting ILD, and these patients have a high risk of developing chemotherapy-induced ILD. In addition, patients with DILD who underwent EGFR-TKI therapy and 2 or more prior chemotherapy regimens had a higher risk of fatal outcome.