Tumor necrosis factor-alpha (TNF-alpha) is an important proinflammatory cytokine. Recently, pentoxifylline (POF) has been shown to suppress the synthesis of TNF-alpha from lipopolysaccharide (LPS)-stimulated human monocytes in cell cultures and in vivo. The aim of this study was to investigate whether POF-induced suppression of TNF-alpha secretion affects peripheral blood monocytes (PBM) and alveolar macrophages (AM) equally, and whether POF is able to suppress the spontaneous TNF-alpha production from AM in pulmonary sarcoidosis in vitro. In seven patients without interstitial lung disease we studied the effect of POF on LPS-stimulated PBM and AM cultured for 24 h. In six patients with sarcoidosis we investigated the effect of POF on the enhanced spontaneous TNF-alpha production by AM in vitro. POF induced a dose-dependent suppression of the LPS-stimulated TNF-alpha production which was not different for PBM and AM, respectively. In sarcoidosis, POF inhibited the spontaneous TNF-alpha production of AM at 0.1 mM by 91% and at 1 mM by 98%. In conclusion, POF inhibits LPS-induced TNF-alpha production from PBM and AM to a similar extent and can also inhibit the exaggerated spontaneous TNF-alpha production from AM in sarcoidosis in vitro. This may be the basis for further clinical trials to evaluate POF as an immunotherapeutic agent in sarcoidosis.

Prolidase deficiency is a rare, inherited disorder characterized by ulceration of the skin, mental retardation, and massive urinary excretion of imidodipeptides. Most patients also have recurrent infections, an unusual facial appearance, and splenomegaly. We describe a girl presenting with chronic dermatitis, recurrent respiratory tract infections since her first months of life, and facial features characteristic of prolidase deficiency. The diagnosis of prolidase deficiency was made at 4.5 months of age. The immunologic study in this patient showed an extreme and progressive increase of total immunoglobulin E (IgE) in serum (reaching the value of 77,600 IU/l) and defective chemotactic function of the neutrophils. Treatment with a hyper-proteic diet supplemented with ascorbic acid, manganese chlorite, and topical proline resulted in reduction of the frequency and severity of the infections and significant improvement of the skin lesions. The authors discuss the immunologic alterations and the favorable evolution with treatment in this patient. PMID:12000488 [PubMed -indexed for MEDLINE]http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2012000488%20 06-07-2011 11:08:32

Alveolar macrophages (AM) from smokers contain characteristic smoker's inclusion bodies within the cytoplasm as a result of ingestion of substances in the inhaled smoke. How long these smoking-related changes in the AM population can be seen after smoking cessation is largely unknown. We had the unique opportunity to investigate a 51-yr-old never-smoker after single lung transplantation (TX) for alpha 1-antitrypsin deficiency emphysema who received a donor's lung from a heavy cigarette smoker. Serial bronchoalveolar lavage (BAL) was performed in the donor's lung for transplant surveillance at defined time intervals, and the percentage of AM with characteristic smoker's inclusions was counted on slides stained with May-Grünwald-Giemsa stain. The patient had an uneventful course after TX with no major infectious complications or episodes of rejection. One month after TX the percentage of smoker's AM was 98%. BAL after 2, 5, 7, and 12 mo showed a similar high percentage. After 18 mo a first a decrease was seen, down to 78%, and after 2 yr a decrease to 59% was seen. After 3 yr, the smoker's AM had mostly disappeared, only 3% were still present. In conclusion, smoker's inclusions in AM may be detected for at least 2 yr after smoking has ceased, which is considerably longer than the estimated life span of the AM.