To the Editor:

The amount of new information in medicine and biology is increasing at a staggering rate. Accessing a necessary piece of information thus may become a challenge, sometimes as significant as generating the data anew. Sophisticated search engines, such as PubMed, utilize sets of search fields and Boolean operators to aid in searches for clinical and research publications.

Even in such databases, composing a complex search request may be a challenge in itself. Inadvertent omission of a search term or a logical operator can significantly limit the scope of a search or lead to noninterpretable results, whereas inclusion of an unnecessary search term can generate a large set of irrelevant hits. Common practice suggests, however, that an individual often repeats searches with only a few search-to-search variations in the composition of the search requests. Similarly, researchers with a common area of interests are likely to compose similar search requests. Preserving the search patterns from previous searches eliminates the need for “reinventing” these patterns every time a new complex search has to be conducted. Presented here is a Web-based tool that aids in systematic searches for research literature on cytokine involvement in tissue fibrosis available through PubMed.

Tissue fibrosis can be a debilitating and sometimes fatal consequence of injury, infection, inflammation, or environmental exposures. Lung fibrosis alone can be a major cause of death in such conditions as scleroderma lung disease, idiopathic pulmonary fibrosis, radiation- and chemotherapy-induced lung fibrosis, rheumatoid arthritis, graft-versus-host disease after bone marrow transplantation, and conditions caused by occupational inhalation of dust particles. Fibrosis develops as a result of accelerated fibroblast proliferation and excessive production of extracellular matrix components, such as collagen, by fibroblasts. Cytokine networks, which are intricate and redundant, regulate activities of fibroblasts (Atamas SP. Complex cytokine regulation of tissue fibrosis. Life Sci 2002;72:631–43). The research literature on this subject, particularly regarding regulation of fibrosis by cytokines, is abundant and often inconsistent, making compilation of literature references a challenge.

I have developed a Web tool that aids in PubMed searches for literature on cytokines and cells involved in tissue fibrosis. The tool consists of 3 PHP scripts, named FCP (Fibrosis-related Cytokines on PubMed), CLF (Cells of Lung Fibrosis), and SLD (Scleroderma Lung Disease–related cytokines and cells). These scripts generate complex search patterns for reports on previously identified profibrotic and antifibrotic cytokines and their cellular sources, and the effects of these cytokines on fibroblasts and tissues. The user can also perform custom searches for new fibrosis-related factors not listed in the tool.

The FCP tool, available at, consists of a table that is being newly generated every time a user accesses it (Figure 1). The searches are initiated by clicking on the buttons in the cells of the table. The table is organized into rows and columns; the rows represent the cytokines of interest, and the columns define the scope of the search.

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Figure 1. The interface of the FCP tool (Fibrosis-related Cytokines on PubMed; Searches are conducted by clicking on the buttons in the cells of the table.

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The rows of the table represent individual cytokines that have been reported to be involved in regulation of fibroblast activities, particularly proliferation and collagen production. These cytokines have been selected as a result of extensive searches. Only those cytokines that have or might have direct effects on fibroblasts, through binding to a specific cell surface receptor, initiating intracellular signal transduction, and finally, exerting functional activities, have been selected. Cytokines that promote tissue fibrosis indirectly, through attracting inflammatory cells, have not been specifically included, in order to make the tool more focused. Also, I have not included cytokines that are more involved during embryonic development rather than in fibrosis in adult tissues, such as fibroblast growth factors and bone morphogenetic proteins. However, the tool also allows the user to conduct a search for a cytokine of his or her interest.

The columns of the table define the scope of searches through the PubMed database for each cytokine, as follows (Figure 1). In columns 1 and 2, the scope of the searches is limited to the effects of the selected cytokines on fibroblasts, including fibroblast proliferation, collagen production, chemotaxis, and phenotypic transformation into myofibroblasts. The difference between columns 1 and 2 is that in column 1 the searches are limited to the article titles, whereas in column 2 both titles and abstracts of the publications are considered. In the next 2 columns, the scope of the searches is much wider, from fibroblasts as a cell type to the overall fibrotic processes in organs and tissues. The searches are either limited to review articles (column 3), or not limited at all, thus providing large sets of hits (column 4). The final column, column 5, was introduced for convenience and searches for general reviews on the cytokine of interest, irrelevant to fibrotic processes. All searches are limited to reports published in the English language. Users who are well acquainted with the PubMed search rules will find more details by analyzing the search strings generated by the tool.

Two similar scripts, CLF ( and SLD ( address more specific fibrotic conditions, i.e., lung fibrosis in general and scleroderma lung disease, respectively. The former script assists in reference searches for reports regarding cells related to lung fibrosis in various diseases, whereas the latter focuses on cytokines and cells at sites of fibrosis in scleroderma, particularly lung fibrosis.

The tool is updated regularly, and new columns and rows will be added to all 3 scripts in the future. Users are invited to suggest new cytokines or search patterns. These PHP scripts are designed in such a way that a new cytokine is added by updating the code with a single line containing the synonyms for the cytokine. This tool should be helpful to scientists and clinicians investigating the mechanisms of tissue fibrosis.

Sergei P. Atamas MD, PhD*, * University of Maryland School of Medicine Baltimore, MD.