Cytokine Networks in the Regulation of Inflammation and Fibrosis in the Lung (Part 2)

In: Pulmonary function

8 Nov 2012

Before one can understand the abnormalities in the regulation of inflammation and fibrosis in patients with pulmonary disease, one must understand the processes regulating inflammation and fibrosis in normal subjects. To accomplish this, we have been studying the ways mononuclear cells and fibroblasts communicate in the normal lung. Studies from this and other laboratories have demonstrated that interleukin-1 (IL-1), tumor necrosis factor (TNF), gamma interferon (IFN-7), and interleuldn-6 (IL-6) play important roles in this communication. Thus, we have focused on these moieties in our studies of the cytokine network regulating inflammatory and fibrotic events in the lung. These studies clearly demonstrate the existence of complex regulatory networks maintaining normal lung homeostasis. They also provide a testable hypothesis that explains the unique anatomy of granulomas and abscesses.
Cytokine Regulation of Fibroblast Function Fibroblast Proliferation
Fibroblasts can be quiescent or rapidly proliferating at different times in the healthy and diseased human lung. Thus, to understand the processes regulating fibroblast proliferation we assessed the regulatory effects of rIL-1 (a and p), rTNF and rIFN-7 on quiescent and rapidly proliferating human lung fibroblasts. Individually rIL-1, rTNF, and rIFN-7 stimulated the proliferation of quiescent cells (Table 1). In all cases, these effects were dose-dependent and were neutralized by preincubating each cytokine with its respective neutralizing anticytokine antibody. Individually rIL-1 (a and P) and rTNF also stimulated the proliferation of rapidly dividing cells. In contrast, rINF-7 caused a dose-dependent inhibition of the proliferation of rapidly dividing cells (Table 1). These studies demonstrate that a single cytokine, in this case rIFN-7, can have different effects depending on the state of activation of the target cell. buy levaquin online

Table I—Recombinant Cytokine Regulation of Fibroblast Proliferation 

Fibroblast

Culture

Conditions

3H-Tdr

Incorporationf

A. Control

427 ±34

rIL-1

3,714 ±271

rTNF

2,177 ±187

rIFN-7

2,375 ±105

B. Control

18,417± 1,011

rIL-1

25,779 ±2,312

rTNF

22,184± 1,044

rIFN-7

12,171 ±1,151

rIL-l + rTNF

13,315 ±1,271

rIFN-7 + rTNF

9,171 ±866


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