Fibrosis pulmonary

Fibrosis is often a normal response to tissue injury where the damaged cells of an organ are unable to regenerate. An example of this is seen in the heart following myocardial infarction, where the infiircted tissue is replaced by a strong fibrous scar. However there are many pathological conditions where the development of fibrosis is detrimental. The fibrotic tissue response of chronic inflammation is often associated with increased numbers of mast cells, and has been most extensively studied in pulmonary fibrosis and systemic sclerosis. 

Expansion of myofibroblasts (gDGE (Growth, Fibrocyte recruitment, EMT) 

MICHAEL P. KEANE, JOHN A. BELPERIO, and ROBERT M. STRIETER 

Marcel Dekker, Inc. 270 Madison Avenue, New York, New York 10016 

The pathogenesis of pulmonary fibrosis is presumably related to initial loss of alveolar type I epithelial cells and endothelial cells. However, the dysregulated repair of pulmonary fibrosis is followed by persistence of inflammation. This is followed by proliferation of type II cells, recruitment and proliferation of endothelial cells and fibroblasts, and deposition of extracellular matrix leading to end-stage alveolar and interstitial fibrosis. These events involve the complex and dynamic interplay between diverse immune effector cells and cellular constituents of the alveolar-capillary membrane and interstitium of the lung. Interaction of these diverse cell populations and the cytokines that they produce culminate in chronic inflammation, angiogenesis, fibroproliferation, and deposition of extracellular matrix. 

Although not all inflammatory disorders result in fibrosis, fibrotic responses are always preceded and potentially perpetuated by chronic inflammation. The salient feature of chronic inflammation is the association of leukocyte infiltration. These recruited leukocytes contribute to the pathogenesis of chronic inflammation, and promote fibrosis via the elaboration of a variety of cytokines. The maintenance of leukocyte recruitment during inflammation requires intercellular communication between infiltrating leukocytes and the endothelium, resident stromal cells, and parenchymal cells. These events are mediated via the generation of early response cytokines, e.g., IL-1 and TNF, the expression of cell surface adhesion molecules, and the production of chemotactic molecules, such as chemo-kines. 

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Epidemiological studies of nickel-producing and nickel-using workers seldom indicate excess mortaUty from nonmalignant respiratory disease. Evidence for such effects exists mainly as a few reports of isolated incidents of asthma, pulmonary fibrosis, chronic bronchitis, and emphysema in nickel workers. Nickel may or may not play a causal role in these incidents (131). 

The principal health hazard that may be associated with shicon and shicon alloys is caused by the crystalline form of the oxide, ie, quartz, used as a raw material. Shica ia its crystalline form is the chief cause of disabling pulmonary fibrosis, such as shicosis. Over a period of years, the breathing of air containing excessive amounts of crystalline shica can cause shortness of breath (30). 

The inorganic tin compound that has received the most study from a toxicological viewpoint is stannic oxide. Autopsies performed on workers in the tin mining and refining industry, who inhaled tin oxide dust for as long as 20 yr, disclosed no pulmonary fibrosis (57). Inhalation for long periods produces a benign, symptomless pneumoconiosis with no toxic systemic effects (58). 

Abbadie C, Lindia JA, Cumiskey AM, Peterson LB, Mudgett JS, Bayne EK, DeMartino JA, MacIntyre DE, Forrest MJ (2003) Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2. Proc Natl Acad Sci USA 100 7947-7952 Agostini C, Gurrieri C (2006) Chemokine/cytokine cocktail in idiopathic pulmonary fibrosis. Proc Am Thorac Soc 3 357-363... 

Scotton CJ, Chambers RC (2007) Molecular targets in pulmonary fibrosis the myofibroblast in focus. Chest 132 1311-1321... 

Forkert PG, Forkert L. 1994. Trichloroethylene induces pulmonary fibrosis in mice. Can J Physiol Pharmacol 72 205-210. 

Cantin, A.M., North, S.L., Fells, G.A., Hubbard, R.C. and Crystal, R.G. (1987). Oxidant mediated epithelial cell injury in idiopathic pulmonary fibrosis. J. Clin. Invest. 79, 1665-1675. 

Mineral dust-induced ROMs contributes to pulmonary fibrosis, malignancy, hypersensitivity and emphysema (Doelman etctl., 1990 Kamp etui., 1992). The involvement of ROMs in pulmonary fibrotic reactions is indicated by the participation of PMN oxidants in the autoactivation of latent coUagenase (Weiss et al., 1985). Prolyl hydroxylase, a key enzyme in collagen fibril formation, has been shown to be dependent on the reaction of superoxide with prolyl residues (Myllyla et al., 1979). 

Direct entry of alumina adjuvants through the skin may occur by the use of therapeutic vaccines, with a resultant transient uptake of aluminium in the brain (Redhead et al., 1992). The injection of talc (magnesium silicate)-containing drugs intended for oral consumption has been shown to induce progressive pulmonary fibrosis in drug abusers (Pare etal., 1989). 

IP4 Inositol tetrakisphosphate IPF Idiopathic pulmonary fibrosis IPO Intestinal peroxidase IpOCOCq Isopropylidene OCOCq I/R Ischaemia-reperfusion IRAP IL-1 receptor antagonist protein IRF-1 Interferon regulatory factor 1 la Short-circuit current ISCOM Immune-stimulating complexes... 

Amiodarone IV Hypotension, sinus bradycardia Oral Blue-grey skin discoloration, photosensitivity, corneal microdeposits, pulmonary fibrosis, hepatotoxicity, sinus bradycardia, hypo- or hyperthyroidism, AV block... 

Bleomycin Antitumor antibiotic Renal clearance Pulmonary fibrosis... 

For bleomycin-containing regimens, total the cumulative dosage received by the patient to monitor for pulmonary fibrosis. 

Melphalan (Alkeran) Myelosuppression, secondary malignancies, pulmonary fibrosis, sterility, alopecia Dose of 0.15 mg/kg for 7 days given orally once daily, repeated every 4-6 weeks IV formulation used for stem cell transplantation... 

Cor pulmonale Right-sided heart failure, usually due to structural lung disease (e.g., pulmonary fibrosis or emphysema). 

Moore BB, Paine R 3rd, Christensen PJ, et al. Protection from pulmonary fibrosis in the absence of CCR2 signaling. J Immunol 2001 167(8) 4368M377. 

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