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As respiratory symptoms are common in addition to skin reactions in natural rubber latex allergy, we investigated the significance of different allergen exposure routes in the development of lung inflammation and airway hyperreactivity (AHR). Both intracutaneous (IC) and intraperitoneal (IP) exposure followed by airway challenge with latex proteins induced an influx of mononuclear cells and eosinophils to the lungs. AHR and lung mucus production increased significantly after IC and IP but not after intranasal (IN) exposure. Infiltration of inflammatory cells was associated with the induction of T-helper type 2 (Th2) cytokines and several CC chemokines. Only a marginal induction of these mediators was found after IN exposure. On the contrary, increased levels of transforming growth factor-beta1 and forkhead box 3 mRNA, markers of regulatory activities, were found in the lungs after IN but not after IC exposure. Finally, IC and IP, but not IN, latex exposure induced a striking increase in specific immunoglobulin E (IgE) levels. Cutaneous latex exposure in the absence of adjuvant followed by airway challenge induces a local Th2-dominated lung inflammation and a systemic IgE response. Cutaneous exposure to proteins eluting from latex products may therefore profoundly contribute to the development of asthma in latex allergy.

Background: Mast cell accumulation and activation have been demonstrated in the vulnerable shoulder regions of atherosclerotic plaques and at the actual sites of plaque erosion and rupture. When activated and degranulated, mast cells release tryptase, a neutral protease, capable of activating matrix metalloproteinases and predisposing to plaque rupture. We tested the hypothesis that in acute coronary syndromes the levels of serum tryptase would reflect mast cell activation., Methods and Results: The study population consisted of 183 patients admitted to the emergency room of 3 general hospitals because of acute chest pain of ischemic origin. Of these patients, 64 suffered from exertional angina presenting with acute chest pain, 60 had unstable angina, and 59 had acute myocardial infarction. Serum tryptase levels were analyzed from samples drawn, on average at 7 h, and also at 24 h after the onset of the chest pain. As controls served 41 patients admitted for surgical treatment of inguinal hernia or varicose veins. Serum tryptase levels remained stable within the observation period, and no differences were detected between the patient groups and controls. On the other hand, the differences in C-reactive protein levels reflected the extent of myocardial injury., Conclusions: In ACS, serum tryptase levels are normal and remain stable. Our results do not exclude the possibility of local activation of coronary mast cells, but suggest that the excess quantity of tryptase acutely released from mast cells in ACS, if any, is not sufficient to be detected by measuring tryptase concentration in the systemic circulation.

Periodontitis, a consequence of persistent bacterial infection and chronic inflammation, has been suggested to predict coronary heart disease (CHD). The aim of this study was to investigate the impact of periodontitis on HDL structure and antiatherogenic function in cholesterol efflux in vitro. HDL was isolated from 30 patients (age 43.6 +/- 6.1 years, mean +/- SD) with periodontitis before and after (3.2 +/- 1.4 months) periodontal treatment. The capacity of HDL for cholesterol efflux from macrophages (RAW 264.7), HDL composition, and key proteins of HDL metabolism were determined. After periodontal treatment, phospholipid transfer protein (PLTP) activity was 6.2% (P<0.05) lower, and serum HDL cholesterol concentration, PLTP mass, and cholesteryl ester transfer protein activity were 10.7% (P<0.001), 7.1% (P=0.078), and 19.4% (P<0.001) higher, respectively. The mean HDL2/HDL3 ratio increased from 2.16 +/- 0.87 to 3.56 +/- 0.48 (P<0.05). HDL total phospholipid mass and sphingomyelin-phosphatidylcholine ratio were 7.4% (P<0.05) and 36.8% (P<0.001) higher, respectively. The HDL-mediated cholesterol efflux tended to be higher after periodontal treatment; interestingly, this increase was significant (P<0.05) among patients whose C-reactive protein decreased (53.7% reduction, P=0.015) and who were positive by PCR for Actinobacillus actinomycetemcomitans. These results suggest that periodontitis causes similar, but milder, changes in HDL metabolism than those that occur during the acute-phase response and that periodontitis may diminish the antiatherogenic potency of HDL, thus increasing the risk for CHD.

In addition to immediate type I allergy symptoms, natural rubber latex allergy may manifest as protein contact dermatitis on the hands of health-care workers and other natural rubber latex glove users. We examined whether repeated application of natural rubber latex on mouse skin causes sensitization to natural rubber latex and dermatitis. Epicutaneous sensitization with natural rubber latex produced a significant influx of mononuclear cells, CD4+ CD3+ cells, and eosinophils to the sensitized skin sites. The number of degranulated mast cells in natural rubber latex-sensitized skin sites was significantly higher compared with control sites treated with phosphate-buffered saline. The expression of interleukin-1beta and interleukin-4 mRNA was markedly increased in natural rubber latex-sensitized skin sites. Moreover, significant increases in the mRNA expression of chemokines CCL2 (monocyte chemoattractant protein-1), CCL11 (eotaxin-1), CCL3 (macrophage inflammatory protein-1alpha), and CCL4 (macrophage inflammatory protein-1beta) were found. In addition to the cutaneous inflammatory response, epicutaneous sensitization with natural rubber latex induced a striking increase in the total and specific immunoglobulin E levels but not in the immunoglobulin G2a levels. Intraperitoneal immunization with natural rubber latex induced a strong natural rubber latex-specific immunoglobulin G2a response, but only a weak immunoglobulin E response. We also studied the role of two major natural rubber latex allergens, the highly hydrophilic prohevein and the hydrophobic rubber elongation factor. Cutaneous application of natural rubber latex elicited a strong immunoglobulin E response against prohevein, but not against rubber elongation factor. On the contrary, intraperitoneal immunization with natural rubber latex elicited strong immunoglobulin G2a production to rubber elongation factor but not to prohevein. These results demonstrate that epicutaneous sensitization with natural rubber latex induces T helper 2-dominated dermal inflammation and strong immunoglobulin E response in this murine model of natural rubber latex induced protein contact dermatitis. Epicutaneous sensitization to natural rubber latex proteins eluting from latex gloves may therefore contribute to the development of hand dermatitis and also natural rubber latex-specific immunoglobulin E antibodies.

Recent data suggest that infections, inflammation and the immune system are involved in the process of atherosclerosis. The aim of the present study was to analyze the association of coronary heart disease (CHD) with three inflammation markers, C-reactive protein (CRP), serum amyloid-A (SAA) and plasma fibrinogen. The cross-sectional study included 1400 men aged 45-74 years, who participated in a cardiovascular risk factor survey in Finland in 1997. Participants with prevalent CHD had markedly higher CRP, SAA and fibrinogen levels than participants without CHD. In logistic regression models, the age, smoking, serum cholesterol and systolic blood pressure adjusted odds ratios (2nd, 3rd and 4th quartile as compared with the 1st quartile) of CHD increased gradually with increasing quartile of CRP (1.90, 2.27, 2.64), SAA (1.68, 1.83, 2.41), and fibrinogen (1.60, 1.95, 2.14). The associations weakened somewhat after further adjustment for indicators of obesity, particularly waist hip-ratio. CRP, SAA and fibrinogen levels were markedly lower among CHD patients using cholesterol-lowering medication as compared to non-users. In conclusion, CRP, SAA and fibrinogen, which are markers of inflammation, were positively and significantly associated with prevalent CHD. Central obesity needs to be considered as a confounding factor in the observed associations. These findings support the hypothesis that cholesterol-lowering drugs have an anti-inflammatory effect.

Endothelium plays a pivotal role in the regulation of vascular relaxation. Inflammation may in turn induce endothelial dysfunction and thus increase the risk of atherothrombosis. We investigated 31 men with angiographically verified coronary heart disease, aged 57. 7+/-5.3 years, in regard to endothelium-dependent, acetylcholine-induced, and to endothelium-independent, sodium nitroprusside-induced vasodilatation in the forearm vasculature by strain-gauge plethysmography. Logistic regression analysis served to determine the relation between forearm vascular function and the inflammatory factors measured, concentration of C-reactive protein, subtypes of peripheral blood T-lymphocytes, and other factors potentially affecting endothelial function (lipoprotein and glucose levels). Concentration of C-reactive protein was an independent determinant of endothelium-dependent vascular function (P<0.001 for low dose acetylcholine, P=0.01 for high dose acetylcholine). Other determinants of endothelium-dependent vascular dysfunction were CD8-lymphocytes expressing ICAM-1 (P=0.001), antibodies to oxidized low-density lipoprotein (P<0.001), and body weight (P=0.007). The present data showed an association between inflammatory risk factors linked to atherothrombosis and endothelial dysfunction in coronary heart disease patients. It is possible that endothelial dysfunction in coronary heart disease patients is related to the chronic inflammation or infection coexisting with atherosclerosis.

Proteins and allergens in natural rubber latex were characterized by a two-dimensional immunoblot method with serum samples from 17 patients with latex allergy of whom 10 had spina bifida and 7 were health care workers. We demonstrated in rubber tree sap approximately 240 polypeptides of which 57 bound immunoglobulin E (IgE) in patient serum samples. Forty-six of the 57 allergens were identified by patients with spina bifida, 19 of 57 allergens by health care workers, and 8 of 57 allergens by both patient groups. IgE antibodies from all 5 patients with spina bifida with histories of anaphylaxis bound three allergens with molecular weights of 27 kd and isoelectric points ranging from pH 4.6 to pH 4.8. Four of these 5 patients also identified a complex of eight other allergens with molecular weights ranging from 13 kd to 27 kd and isoelectric points from pH 4.4 to pH 5.6. This cluster of 11 allergens was identified by none of the 7 health care workers and by only 1 of 5 patients with spina bifida without demonstrable anaphylaxis. These preliminary findings indicate that patients with spina bifida in whom latex hypersensitivity has developed exhibit a strong anti-latex IgE immune response, which seems to differ markedly from the immune response of health care workers with latex allergy. The characteristic anti-latex IgE profile in patients with spina bifida and with a history of an anaphylactic reaction may be valuable in the evaluation of pathogenetic processes in latex allergy.

Serum lipoproteins contain phospholipids and modified low-density lipoprotein (LDL) may thus act as a target for antiphospholipid antibodies. Raised concentrations of IgG antibodies against oxidised LDL were found in 47 of 61 (80%) patients with systemic lupus erythematosus (SLE). 46% of patients also had raised concentrations of IgG anticardiolipin antibodies. Binding of anticardiolipin antibodies to solid-phase cardiolipin was inhibited by oxidised LDL but not by native LDL in 16 of 21 sera from SLE patients. These observations suggest crossreactivity between antiphospholipid antibodies, which are closely associated with thrombosis in SLE, and antibodies to oxidised LDL, thus providing a possible link between thrombotic and atherosclerotic complications in SLE.

IgG rheumatoid factors were demonstrated by enzyme immunoassay using, as antigen, goat antibodies to human serum albumin in the form of immune complexes. Elevated levels of IgG rheumatoid factor were noted in the majority of patients with seropositive rheumatoid arthritis but also relatively often in normal blood donors. Reactivity of IgG rheumatoid factor was in most instances inhibitable by IgG from various species, including man. Exceptionally, restricted specificity towards IgG from bovidae, was recognized.