**2.4 Chronic obstructive pulmonary disease (COPD)**

COPD is a chronic inflammatory lung disease triggered by exposure to toxic particles and gases, especially, cigarette smoke. Some of the predominant characteristics of COPD include parenchymal destruction, poorly reversible, persistent airflow limitation, and chronic bronchitis. A COPD patient shows some visible symptoms like cough, chest tightness dyspnoea, excess sputum production, and wheezing [52]. COPD is coordinated by a complex network of inflammatory mediators, such as inflammatory enzymes, lipid mediators (eicosanoids, namely prostanoids and leukotrienes, LTs), interleukins (ILs), and adhesion molecules, which may moderate airway inflammation through chemotactic and autocrine or paracrine effects [3]. Eicosanoids are produced by cells resident in the lung and airways, such as fibroblasts, epithelial cells, myofibroblasts, and smooth muscle cells, also by inflammatory cells that have migrated from the circulation to the airways, such as macrophages, mast cells, neutrophils, platelets, eosinophils, and T-lymphocytes [53]. Activated macrophages release cytokines such as IL-8, IL-6, IL-10, TNF-α, and LTB4, which can attract and activate various inflammatory cells. Smooth muscle cells, fibroblasts, and myofibroblasts play a key regulatory role in airway remodeling by generating different structural components, such as collagen and proteoglycans [54]. Although the mediators involved in structural remodeling of the bronchial wall remains unknown, chemokines, cytokines, and growth factors are thought to have a crucial role. Observational clinical studies suggest that n-3 PUFA levels in COPD are inversely related to systemic inflammation and directly related to clinical outcomes [55–57]. Interventional studies using n-3 PUFAs alone in COPD do not exist; however, many trials are currently underway, which may generate valuable data in the coming years [58–60]. An animal study in pneumonia model of mice, revealed RvE1 metabolite of n-3 PUFA decreased levels of several pro-inflammatory chemokines and cytokines in the lung, and improved survival [61]. However, currently, there is a paucity of data regarding the potential of n-3 PUFAs to be used therapeutically in COPD. Recent studies, conducted using omega-3 PUFAs in COPD has used nutrient combinations, in a manner that the exact effects of omega-3 PUFAs cannot be elucidated.

### **2.5 Rheumatoid arthritis**

Rheumatoid arthritis (RA) is a low grade chronic inflammatory autoimmune disease affecting the joints and bones. RA and systemic lupus erythematosus (SLE) are multisystem autoimmune diseases featuring the production of a variety of autoantibodies, and resulting in higher immune-mediated inflammation. Prevalence of RA is known to affect 17.6 million people worldwide [7] with the huge economic burden to mankind. Pathogenesis of RA in early phase focused on auto-antibodies and immune complexes [62], however, the nature of T-cell mediated antigen-specific responses, T-cell-independent cytokine species, and aggressive tumor-like behavior of rheumatoid synovium have also been reported. Immune complex theory strongly suggests increased neutrophils accumulation in synovial fluid results in engulfment of immune complex and release proteolytic enzymes [62]. A better understanding of the intracellular targets that regulate cytokines in RA can potentially lead to new therapeutic interventions. For instance, studies reported activation of NF-κB in the synovium of RA patients [63] and mitogen-activated protein (MAP) kinases are identified as vital regulators of cytokine and metalloproteinase production. The mechanistic approach to currently available drugs is partially understood and mostly targeting the eicosanoid pathway, and reports are scarce about gene targets on CD28, AP-1, and MAP kinases. Investigators have examined the effect of dietary fatty acid supplementation in different autoimmune diseases, and the effects of both n-6 and n-3 PUFA on RA have been reported [64]. Resolvins derived from EPA and DHA are anti-inflammatory and resolve inflammation, serving as important mediators in regulating various homeostatic functions, including gastric mucosal integrity. Kremer and co-workers reported that a dose of 90 mg/kg/day EPA/DHA (3:2 ratio) showed a shorter period to respond than 45 mg/kg/day [65]. Clinical studies have ambiguity in results, few observed reductions in both tender joints by 36% and swollen joint to 38% in patients, whereas the placebo group showed no improvement in these parameters [66]. Fish oil supplementation in women patients showing a decrease in the production of serum nuclear factor-kappa B (Nf-kB) ligand/osteoprotegerin ratio [67]. Cell culture-based investigations have reported that EPA and DHA prevent the proliferation of human T cells and their generation of IL-2 [68]. Animal studies also reported a beneficial effect of marine n-3 PUFA in RA [69, 70]. Finally, supplementation with dietary n-3 PUFA and its ability to inhibit TNF-α and IL-1b synthesis is rational. Considering the emphasis on recommendations to increase dietary n-3 PUFA intake for health benefits, the possible therapeutic potential of fish oil/n-3 PUFA on autoimmune diseases need to be clearly defined.

**203**

*Modulatory Potentials of n-3 Polyunsaturated Fatty Acids in Inflammatory Diseases*

Conjunctivitis is an ocular inflammatory condition of the membrane lining the eyelid, which provides a shelter to the open surface of the sclera [71]. It is said to be the most common cause of "red eye," and the infection, either acute or chronic can originate from three different sources, based on which it is commonly classified: viral, allergic, and bacterial conjunctivitis. The type of conjunctivitis may be determined by a diagnostic investigation which takes into account, the patient's age, time of the year, and physical examination findings [72]. Identification of the pathogen which elicits the inflammatory response is necessary to decide on the required treatment module, since some bacterial conjunctivitis forms are self-limiting, while those caused by *Chlamydia trachomatis* or *Neisseria gonorrhoeae* demand aggressive antibiotic therapy, and primarily good eyelid hygiene [71]. The visual symptoms of inflammation at the ocular surface, include, lid and conjunctival edema–redness, tearing, extreme itching, and photophobia during the acute phase cause immense discomfort, thereby necessitating treatment [73]. Effective pharmacological cure comprises antihistamines, mast cell stabilizers, and non-steroidal anti-inflammatory drugs [74]. The excess wateriness experienced during conjunctivitis and also early dry eye disease is because of enhanced goblet cell mucin secretion into tears, which otherwise produce a regulated amount of mucins only to protect the eye. This phenomenon is due to the action of inflammatory mediators, cysteinyl leukotrienes LTB4, LTC4, LTD4, and LTE4, and prostaglandin PGD2, which stimulate conjunctival goblet cell mucous secretion. Thus, mitigation of this LTD4 effect can aid in reducing mucin secretion, and this has been achieved previously by the action of Resolvins D1 (RvD1) and E1 (RvE1) [2]. The finding of Dartt and co-workers [2] indicates that lipids including fatty acids or lipid mediators play a role in suppression of systemic inflammation as well as local, such as in the case of inflammatory conjunctivitis. The connection between the quality of fat consumed and conjunctivitis was drawn from the results of a Japanese study, which states that meat intake is directly proportional to the prevalence of rhinoconjunctivitis in young adult Japanese women, while no correlation was seen between fish intake and rhinoconjunctivitis [75]. Though, there are not many reports from similar controlled clinical trials that specifically correlate meat intake with incidence of conjunctivitis, to ascertain such claims. The study does raise questions on the role of fats present in meat that possibly trigger the pathways in inflammation. The true potential of n-3 PUFA as an anti-inflammatory in managing conjunctivitis was elucidated through other detailed investigations of their actions and mechanisms at molecular levels. A primary mode of action is that of the resolvin mediated responses, as mentioned earlier. The process of resolution of inflammation is an active process facilitated by pro-resolution lipid mediators. Not only D-series resolvins RvD1, which are produced in the cornea but also aspirin-triggered RvD1 (ATRvD1) have exhibited regulation of inflammatory responses to histamine in allergic conjunctivitis. The effect is implemented by a cross-talk between two types of G protein-coupled receptors (GPCRs). When RvD1 interacts with its receptor GPR32, it prevents the histamine-stimulated H1 receptor-mediated rise in intracellular Ca2+, thereby blocking H1 receptor-mediated responses. Consequentially, this activates extracellularly regulated–protein kinase (ERK) 1/2 [76]. In addition to resolvins, another class of lipid mediators that can mimic these anti-inflammatory actions in conjunctivitis includes lipoxins, especially, lipoxin A4 that has benefits similar to that of ATRvDI and can activate ALX/FPR2 receptor to regulate conjunctival goblet cell secretion, which is particularly useful in maintaining ocular surface homeostasis, and managing the dry eye syndrome [77]. Another evidence of polyunsaturated fats aiding in the treatment of conjunctivitis emerged on evaluating the impact of the feeding of omega-3 and omega-6 PUFA on human leukocyte antigen-DR (HLA-DR) marker of conjunctival

*DOI: http://dx.doi.org/10.5772/intechopen.88394*

**2.6 Conjunctivitis**
