Intranasal heparin reduces eosinophil recruitment after nasal allergen challenge in patients with allergic rhinitis.

BACKGROUND: Recently, several studies have shown that heparin possesses various anti-inflammatory and antiallergic properties. It has been proposed that heparin might play an important role in limiting the inflammatory events associated with asthma and allergic rhinitis by neutralizing inflammatory mediators, such as eosinophil cationic protein and major basic protein, and by limiting eosinophil recruitment. OBJECTIVE: To test the hypothesis that heparin can limit the extent and magnitude of eosinophilic inflammation, we examined the effect of inhaled intranasal heparin on nasal response to allergen challenge in 10 patients with allergic rhinitis. METHODS: The capacity of heparin to reduce nasal response was studied by evaluating symptom score, eosinophil cationic protein concentration, and eosinophil counts in nasal lavage fluids 10, 60, and 360 minutes after allergen challenge. RESULTS: Pretreatment with intranasal heparin produced a significant reduction in symptom score 10 minutes after allergen challenge and reduced the eosinophil influx at each time point after antigen challenge, statistical significance being reached 60 and 360 minutes after allergen challenge. Similarly, the amount of eosinophil cationic protein in the nasal wash was reduced at each time point; this reached statistical significance 360 minutes after allergic challenge. CONCLUSION: Heparin was shown to provide protection with respect to nasal allergen challenge. The mechanism by which heparin produces its protective activity seems to be related to the neutralization of eosinophil cationic protein as well as to the reduction of eosinophil recruitment.

Human lung fibroblasts inhibit tumor necrosis factor-alpha production by LPS-activated monocytes.

Mononuclear phagocytes are important regulators of normal immune, inflammatory, and fibrotic responses. These functions are mediated through the production of several cytokines, including tumor necrosis factor-alpha (TNF-alpha), which regulate the activity of inflammatory and tissue structural cells such as fibroblasts. It is increasingly evident that fibroblasts are also capable of releasing a number of cytokines and soluble factors that can, in turn, interact with monocytes and thereby modulate the inflammatory process. In this study we provide evidence that human lung fibroblasts, through the release of soluble factors such as prostaglandin E2 (PGE2), inhibit both TNF messenger ribonucleic acid (mRNA) accumulation and TNF-alpha protein release by lipopolysaccharide (LPS)-activated human peripheral blood monocytes (PBM). Reverse transcriptase-polymerase chain reaction (RT-PCR) results showed that fibroblast-conditioned medium (FCM) caused a 50% reduction of the TNF-alpha transcript accumulation in LPS-stimulated monocytes. Furthermore, FCM induced a significant decrease in the release of TNF-alpha by LPS-activated PBM. This effect was dependent on the concentration of the FCM and the number of fibroblasts producing it. The maximal effect was seen with monocytes cultured in 100% FCM produced by 2 x 10(6) fibroblasts. This indicated that one or possibly more soluble factors released by fibroblasts were responsible for the effect. Considering that exogenous PGE2 can inhibit TNF-alpha production by PBM, and that fibroblasts are a good source of PGE2, we determined the content of PGE2 in the FCM used in our experiments. We found a good correlation (r = 0.949) between the amount of PGE2 produced by fibroblasts and the degree of TNF-alpha inhibition exerted. In addition, the inhibitory effect of FCM was mimicked by the addition to PBM cultures of exogenous PGE2 in amounts similar to those spontaneously released by fibroblasts in FCM. All of these data suggest a molecular and cellular interaction between PBM and fibroblasts that could contribute to those modulatory mechanisms involved in the self-limitation of the fibrotic process.