Systemic inflammation in chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) is characterised by a chronic inflammation in the pulmonary tissue. The disease is associated with a switch from a self-limiting inflammatory response, mainly initiated by smoke inhalation, to a chronic persistent inflammatory response after prolonged interaction with cigarette smoke. The extent of the inflammatory reaction is correlated with the severity of the disease.Chronic inflammation in the pulmonary tissue is also associated with systemic effects. These effects range from cytokine-induced priming of peripheral leukocytes, to muscle wasting induced by cytokines such as tumour necrosis factor-a. Despite a general consensus that chronic inflammation is a characteristic phenomenon of the disease, surprisingly little is known regarding the underlying pathogenetic mechanisms.A clear communication is present between the disease mechanisms in the pulmonary compartment and peripheral tissues, leading to the concept of COPD as a systemic inflammatory disease. This communication can be mediated by: 1) leakage of reactive oxygen species and stress-induced cytokines directly into the peripheral blood, 2) (pre)activation of peripheral blood leukocytes that can result in aberrant homing and activation of inflammatory cells in distant tissues, and 3) the liberation of proinflammatory mediators by leukocytes and/or stromal cells present in the pulmonary tissues during progression of the disease.The current authors hypothesise that the occurrence of a chronic inflammatory response after prolonged interaction of the pulmonary tissue with cigarette smoke causes aberrant homing of leukocytes to the tissue and delayed apoptosis. This leads to the autonomous characteristic of the inflammatory response in patients with chronic obstructive pulmonary disease. Eur Respir J 2003; 22: Suppl. 46, 5s-13s.

HNE increases HO-1 through activation of the ERK pathway in pulmonary epithelial cells

“…In this report we show for the first time that HNE induces HO-1 mRNA, protein, and activity in pulmonary epithelial cells. HNE is not only a marker of oxidative stress that is induced by environmental exposure to "pollutants" and in diseases and disorders of the lung with an inflammatory component; it is also a mediator of both injury and adaptive responses [22,24,[52][53][54][55]. The induction of HO-1 by HNE was both rapid and dramatic.…”

Etiología y biomarcadores de inflamación sistémica en las exacerbaciones leves a moderadas de la enfermedad pulmonar obstructiva crónica

“…La inflamación es una condición patológica importante asociada a la EPOC 41 y las manifestaciones clínicas de las exacerbaciones son atribuidas a un aumento de la inflamación local y sistémica gatilladas por las infecciones bacterianas o virales y estímulos no infecciosos tales como la contaminación ambiental 14,[17][18][19][20]35,36 . Se observa un aumento en el recuento de neutrófilos, que explica el esputo purulento, y en la liberación de citoquinas proinflamatorias en la vía aérea (TNFa, IL 6, IL 8, LT B 4 ) 14,42 .…”

“…La EPOC se ha asociado a un estado de inflamación sistémica con aumento de varios biomarcadores séricos, tales como la proteína C reactiva (PCR), interleuquina 6 (IL6) y factor de necrosis tumoral alfa (TNFa); los cuales no serían buenos predictores del riesgo de exacerbación [17][18][19][20] .…”

Differential regulation of TNFα and GM-CSF induced activation of P38 MAPK in neutrophils and eosinophils

“…In these diseases, innate immune cells, such as eosinophils and neutrophils, play an important role in the pathogenesis of chronic persistent inflammatory processes seen in the bronchial tissue (Oudijk et al, 2003;Douwes et al, 2002;Jatakanon et al, 1999;Gibson et al, 2001;Luijk et al, 2005). Therefore, proper regulation of activation of the P38 pathway in eosinophils and neutrophils during the inflammatory processes is required to prevent exaggerated damage to host tissue.…”

“…The cytokines TNF␣ and GM-CSF were investigated in these processes because they use distinct receptors that are expressed on both cell types. In addition, both cytokines have been associated with chronic inflammation in inflammatory diseases, such as asthma and COPD (Oudijk et al, 2003(Oudijk et al, , 2005Thomas, 2001;Ritz et al, 2002).…”