Inflammation and disease progression


Inflammation is a physiological response to a foreign organism such as bacteria, dust particles, and viruses. Recent studies have enlightened the role of inflammation in the progression of a variety of diseases such as cancer, atherosclerosis, asthma, and psoriasis. This article is a brief overview of the inflammatory processes involved in the progression of these common diseases. Knowledge about these mechanisms can shed light into development of newer therapeutic agents that are aimed at the eradication of these diseases.

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  1. 1.

    Janeway, C. A., Travers, P., Walport, M., & Shlomchik, M. (2001). Immunobiology: The immune system in health and disease. London: Taylor & Francis.

  2. 2.

    Coussens, L. M., & Werb, Z. (2002). Inflammation and cancer. Nature, 420, 860–867.

    Article  CAS  PubMed  Google Scholar 

  3. 3.

    Lawrence, T., Willoughby, D. A., & Gilroy, D. W. (2002). Anti-inflammatory lipid mediators and insights into the resolution of inflammation. Nature Reviews. Immunology, 2, 787–795.

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    Nathan, C. (2002) Points of control in inflammation. Nature, 420, 846–852.

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Rossi, D., & Zlotnik, A. (2000). The biology of chemokines and their receptors. Annual Review of Immunology, 18, 217–242.

    Article  CAS  PubMed  Google Scholar 

  6. 6.

    Funk, C. D. (2001). Prostaglandins and leukotrienes: Advances in eicosanoid biology. Science, 294, 1871–1875.

    Article  CAS  PubMed  Google Scholar 

  7. 7.

    Serhan, C. N., & Savill, J. (2005). Resolution of inflammation: The beginning programs the end. Nature Immunology, 6, 1191–1197.

    Article  CAS  PubMed  Google Scholar 

  8. 8.

    Balkwill, F., Charles, K.A., & Mantovani, A. (2005). Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell, 7, 211–217.

    Article  CAS  PubMed  Google Scholar 

  9. 9.

    Coussens, L. M., Tinkle, C. L., Hanahan, D., & Werb, Z. (2000). MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell, 103, 481–490.

    Article  CAS  PubMed  Google Scholar 

  10. 10.

    Lu, H., Ouyang, W., & Huang, C. (2006). Inflammation, a key event in cancer development. Molecular Cancer Research, 4, 221–233.

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    Pollard, J. W. (2004). Tumour-educated macrophages promote tumour progression and metastasis. Nature Reviews Cancer, 4, 71–78.

    Article  CAS  PubMed  Google Scholar 

  12. 12.

    Jung, Y. J., Isaacs, J. S., Lee, S., Trepel, J., & Neckers, L. (2003). IL-1beta-mediated up-regulation of HIF-1alpha via an NFkappaB/COX-2 pathway identifies HIF-1 as a critical link between inflammation and oncogenesis. FASEB Journal, 17, 2115–2117.

    CAS  PubMed  Google Scholar 

  13. 13.

    Torisu, H., Ono, M., Kiryu, H., Furue, M., Ohmoto, Y., Nakayama, J., et al. (2000). Macrophage infiltration correlates with tumor stage and angiogenesis in human malignant melanoma: Possible involvement of TNFalpha and IL-1alpha. International Journal of Cancer, 85, 182–188.

    CAS  Google Scholar 

  14. 14.

    Schoppmann, S. F., Birner, P., Stockl, J., Kalt, R., Ullrich, R., Caucig, C., et al. (2002). Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis. American Journal of Pathology, 161, 947–956.

    CAS  PubMed  Google Scholar 

  15. 15.

    Steele, R. J., Eremin, O., Brown, M., & Hawkins, R. A. (1984). A high macrophage content in human breast cancer is not associated with favourable prognostic factors. British Journal of Surgery, 71, 456–458.

    CAS  PubMed  Google Scholar 

  16. 16.

    Becker, C., Fantini, M. C., Wirtz, S., Nikolaev, A., Lehr, H. A., Galle, P. R., et al. (2005). IL-6 signaling promotes tumor growth in colorectal cancer. Cell Cycle, 4, 217–220.

    CAS  PubMed  Google Scholar 

  17. 17.

    Locksley, R. M., Killeen, N., & Lenardo, M. J. (2001). The TNF and TNF receptor superfamilies: Integrating mammalian biology. Cell, 104, 487–501.

    Article  CAS  PubMed  Google Scholar 

  18. 18.

    Jaiswal, M., LaRusso, N. F., Burgart, L. J., & Gores, G. J. (2000). Inflammatory cytokines induce DNA damage and inhibit DNA repair in cholangiocarcinoma cells by a nitric oxide-dependent mechanism. Cancer Research, 60, 184–90.

    CAS  PubMed  Google Scholar 

  19. 19.

    Arnott, C. H., Scott, K. A., Moore, R. J., Robinson, S. C., Thompson, R. G., & Balkwill, F. R. (2004). Expression of both TNF-alpha receptor subtypes is essential for optimal skin tumour development. Oncogene, 23, 1902–1910.

    Article  CAS  PubMed  Google Scholar 

  20. 20.

    Knight, B., Yeoh, G. C., Husk, K. L., Ly, T., Abraham, L. J., Yu, C., et al. (2000). Impaired preneoplastic changes and liver tumor formation in tumor necrosis factor receptor type 1 knockout mice. Journal of Experimental Medicine, 192, 1809–1818.

    Article  CAS  PubMed  Google Scholar 

  21. 21.

    Rollins, B. J. (2006). Inflammatory chemokines in cancer growth and progression. European Journal of Cancer, 42, 760–767.

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    Norgauer, J., Metzner, B., & Schraufstatter, I. (1996). Expression and growth-promoting function of the IL-8 receptor beta in human melanoma cells. Journal of Immunology, 156, 1132–1137.

    CAS  Google Scholar 

  23. 23.

    Owen, J. D., Strieter, R., Burdick, M., Haghnegahdar, H., Nanney, L., Shattuck-Brandt, R., et al. (1997). Enhanced tumor-forming capacity for immortalized melanocytes expressing melanoma growth stimulatory activity/growth-regulated cytokine beta and gamma proteins. International Journal of Cancer, 73, 94–103.

    Article  CAS  Google Scholar 

  24. 24.

    Balentien, E., Mufson, B. E., Shattuck, R. L., Derynck, R., & Richmond, A. (1991). Effects of MGSA/GRO alpha on melanocyte transformation. Oncogene, 6, 1115–1124.

    CAS  PubMed  Google Scholar 

  25. 25.

    Libby, P., Ridker, P. M., & Maseri, A. (2002). Inflammation and atherosclerosis. Circulation, 105, 1135–1143.

    Article  CAS  PubMed  Google Scholar 

  26. 26.

    Stoll, G., & Bendszus, M. (2006). Inflammation and atherosclerosis: Novel insights into plaque formation and destabilization. Stroke, 37, 1923–1932.

    Article  CAS  PubMed  Google Scholar 

  27. 27.

    Ross, R. (1999). Atherosclerosis—An inflammatory disease. New England Journal of Medicine, 340, 115–126.

    Article  CAS  PubMed  Google Scholar 

  28. 28.

    Berliner, J., Leitinger, N., Watson, A., Huber, J., Fogelman, A.,& Navab, M. (1997). Oxidized lipids in atherogenesis: Formation, destruction and action. Thrombosis and Haemostasis, 78, 195–199.

    CAS  PubMed  Google Scholar 

  29. 29.

    Han, J., Hajjar, D. P., Febbraio, M., & Nicholson, A. C. (1997). Native and modified low density lipoproteins increase the functional expression of the macrophage class B scavenger receptor, CD36. Journal of Biological Chemistry, 272, 21654–21659.

    Article  CAS  PubMed  Google Scholar 

  30. 30.

    Quinn, M. T., Parthasarathy, S., Fong, L. G., & Steinberg, D. (1987). Oxidatively modified low density lipoproteins: a potential role in recruitment and retention of monocyte/macrophages during atherogenesis. Proceedings of the National Academy of Sciences of the United States of America, 84, 2995–2998.

    Article  CAS  PubMed  Google Scholar 

  31. 31.

    Rajavashisth, T. B., Andalibi, A., Territo, M. C., Berliner, J. A., Navab, M., Fogelman, A. M., et al. (1990). Induction of endothelial cell expression of granulocyte and macrophage colony-stimulating factors by modified low-density lipoproteins. Nature, 344, 254–257.

    Article  CAS  PubMed  Google Scholar 

  32. 32.

    Fidge, N. H. (1999). High density lipoprotein receptors, binding proteins, and ligands. Journal of Lipid Research, 40, 187–201.

    CAS  PubMed  Google Scholar 

  33. 33.

    Arai, T., Wang, N., Bezouevski, M., Welch, C., & Tall, A. R. (1999). Decreased atherosclerosis in heterozygous low density lipoprotein receptor-deficient mice expressing the scavenger receptor BI transgene. Journal of Biological Chemistry, 274, 2366–2371.

    Article  CAS  PubMed  Google Scholar 

  34. 34.

    Braun, A., Trigatti, B. L., Post, M. J., Sato, K., Simons, M., Edelberg, J. M., et al. (2002). Loss of SR-BI expression leads to the early onset of occlusive atherosclerotic coronary artery disease, spontaneous myocardial infarctions, severe cardiac dysfunction, and premature death in apolipoprotein E-deficient mice. Circulation Research, 90, 270–276.

    Article  CAS  PubMed  Google Scholar 

  35. 35.

    Han, J., Parsons, M., Zhou, X., Nicholson, A. C., Gotto, A. M., Jr., & Hajjar, D. P. (2004). Functional interplay between the macrophage scavenger receptor class B type I and pitavastatin (NK-104). Circulation, 110, 3472–3479.

    Article  CAS  PubMed  Google Scholar 

  36. 36.

    Han, J., Zhou, X., Yokoyama, T., Hajjar, D. P., Gotto, A. M., Jr., & Nicholson, A. C., et al. (2004). Pitavastatin downregulates expression of the macrophage type B scavenger receptor, CD36. Circulation, 109, 790–796.

    Article  CAS  PubMed  Google Scholar 

  37. 37.

    Hernandez-Presa, M., Bustos, C., Ortego, M., Tunon, J., Renedo, G., Ruiz-Ortega, M., et al. (1997). Angiotensin-converting enzyme inhibition prevents arterial nuclear factor-kappa B activation, monocyte chemoattractant protein-1 expression, and macrophage infiltration in a rabbit model of early accelerated atherosclerosis. Circulation, 95, 1532–1541.

    CAS  PubMed  Google Scholar 

  38. 38.

    Tummala, P. E., Chen, X. L., Sundell, C. L., Laursen, J. B., Hammes, C. P., Alexander, R. W., et al. (1999). Angiotensin II induces vascular cell adhesion molecule-1 expression in rat vasculature: A potential link between the renin–angiotensin system and atherosclerosis. Circulation, 100, 1223–1229.

    CAS  PubMed  Google Scholar 

  39. 39.

    Kranzhofer, R., Schmidt, J., Pfeiffer, C. A., Hagl, S., Libby, P., & Kubler, W. (1999). Angiotensin induces inflammatory activation of human vascular smooth muscle cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 19, 1623–1629.

    CAS  PubMed  Google Scholar 

  40. 40.

    Yeh, C. H., Sturgis, L., Haidacher, J., Zhang, X. N., Sherwood, S. J., Bjercke, R. J., et al. (2001). Requirement for p38 and p44/p42 mitogen-activated protein kinases in RAGE-mediated nuclear factor-kappaB transcriptional activation and cytokine secretion. Diabetes, 50, 1495–1504.

    CAS  PubMed  Google Scholar 

  41. 41.

    Blankenberg, S., Barbaux, S., & Tiret, L. (2003). Adhesion molecules and atherosclerosis. Atherosclerosis, 170, 191–203.

    Article  CAS  PubMed  Google Scholar 

  42. 42.

    Cybulsky, M. I., Iiyama, K., Li, H., Zhu, S., Chen, M., Iiyama, M., et al. (2001). A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. Journal of Clinical Investigation, 107, 1255–1262.

    CAS  PubMed  Google Scholar 

  43. 43.

    Li, H., Cybulsky, M. I., Gimbrone, M. A., Jr., & Libby, P. (1993). An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium. Arteriosclerosis and Thrombosis, 13, 197–204.

    PubMed  Google Scholar 

  44. 44.

    Collins, R. G., Velji, R., Guevara, N. V., Hicks, M. J., Chan, L., & Beaudet, A. L. (2000). P-Selectin or intercellular adhesion molecule (ICAM)-1 deficiency substantially protects against atherosclerosis in apolipoprotein E-deficient mice. Journal of Experimental Medicine, 191, 189–194.

    Article  CAS  PubMed  Google Scholar 

  45. 45.

    Gu, L., Okada, Y., Clinton, S. K., Gerard, C., Sukhova, G. K., Libby, P., et al. (1998). Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Molecular Cell, 2, 275–281.

    Article  CAS  PubMed  Google Scholar 

  46. 46.

    Smith, J. D., Trogan, E., Ginsberg, M., Grigaux, C., Tian, J., & Miyata, M. (1995). Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E. Proceedings of the National Academy of Sciences of the United States of America, 84(92), 8264–8268.

    Article  Google Scholar 

  47. 47.

    Qiao, J. H., Tripathi, J., Mishra, N. K., Cai, Y., Tripathi, S., Wang, X. P., et al. (1997). Role of macrophage colony-stimulating factor in atherosclerosis: Studies of osteopetrotic mice. American Journal of Pathology, 150, 1687–1699.

    CAS  PubMed  Google Scholar 

  48. 48.

    Mach, F., Sauty, A., Iarossi, A. S., Sukhova, G. K., Neote, K., Libby, P., et al. (1999). Differential expression of three T lymphocyte-activating CXC chemokines by human atheroma-associated cells. Journal of Clinical Investigation, 104, 1041–1050.

    CAS  PubMed  Google Scholar 

  49. 49.

    Libby, P., Geng, Y. J., Aikawa, M., Schoenbeck, U., Mach, F., Clinton, S. K., et al. (1996). Macrophages and atherosclerotic plaque stability. Current Opinion in Lipidology, 7, 330–335.

    CAS  PubMed  Google Scholar 

  50. 50.

    Libby, P., Sukhova, G., Lee, R. T., & Galis, Z. S. (1995). Cytokines regulate vascular functions related to stability of the atherosclerotic plaque. Arteriosclerosis and Thrombosis, 25(Suppl 2), S9–S12.

    CAS  Google Scholar 

  51. 51.

    Luster, A. D., & Tager, A. M. (2004). T-cell trafficking in asthma: Lipid mediators grease the way. Nature Reviews Immunology, 4, 711–724.

    Article  CAS  PubMed  Google Scholar 

  52. 52.

    Wenzel, S. E. (2003). The role of leukotrienes in asthma. Prostaglandins, Leukotrienes and Essential Fatty Acids, 69, 145–155.

    Article  CAS  Google Scholar 

  53. 53.

    Hamid, Q., Tulic, M. K., Liu, M. C., & Moqbel, R. (2003). Inflammatory cells in asthma: mechanisms and implications for therapy. Journal of Allergy and Clinical Immunology, 111, S5–S12; discussion S12–S17.

    Article  CAS  PubMed  Google Scholar 

  54. 54.

    Bradding, P., Walls, A. F., & Holgate, S. T. (2006). The role of the mast cell in the pathophysiology of asthma. Journal of Allergy and Clinical Immunology, 117, 1277–1284.

    Article  CAS  PubMed  Google Scholar 

  55. 55.

    Bradding, P., Roberts, J. A., Britten, K. M., Montefort, S., Djukanovic, R., Mueller, R., et al. (1994). Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: Evidence for the human mast cell as a source of these cytokines. American Journal Respiratory Cell and Molecular Biology, 10, 471–480.

    CAS  Google Scholar 

  56. 56.

    Gordon, J. R., Burd, P. R., & Galli, S. J. (1990). Mast cells as a source of multifunctional cytokines. Immunology Today, 11, 458–464.

    Article  CAS  PubMed  Google Scholar 

  57. 57.

    Li, H., Sim, T. C., & Alam, R. (1996). IL-13 released by and localized in human basophils. Journal of Immunology, 156, 4833–4838.

    CAS  Google Scholar 

  58. 58.

    Liu, M. C., Proud, D., Schleimer, R. P., & Plaut, M. (1984). Human lung macrophages enhance and inhibit lymphocyte proliferation. Journal of Immunology, 132, 2895–2903.

    CAS  Google Scholar 

  59. 59.

    Williams, J., Johnson, S., Mascali, J. J., Smith, H., Rosenwasser, L. J., & Borish, L. (1992). Regulation of low affinity IgE receptor (CD23) expression on mononuclear phagocytes in normal and asthmatic subjects. Journal of Immunology, 149, 2823–2829.

    CAS  Google Scholar 

  60. 60.

    Fuller, R. W., Morris, P. K., Richmond, R., Sykes, D., Varndell, I. M., Kemeny, D. M., et al. (1986). Immunoglobulin E-dependent stimulation of human alveolar macrophages: Significance in type 1 hypersensitivity. Clinical and Experimental Immunology, 65, 416–426.

    CAS  PubMed  Google Scholar 

  61. 61.

    Fuller, R. W. (1989). The role of the alveolar macrophage in asthma. Respiratory Medicine, 83, 177–178.

    CAS  PubMed  Google Scholar 

  62. 62.

    Joseph, M., Tonnel, A. B., Capron, A., & Voisin, C. (1980). Enzyme release and superoxide anion production by human alveolar macrophages stimulated with immunoglobulin E. Clinical and Experimental Immunology, 40, 416–22.

    CAS  PubMed  Google Scholar 

  63. 63.

    Gosset, P., Tsicopoulos, A., Wallaert, B., Joseph, M., Capron, A., & Tonnel, A. B. (1992). Tumor necrosis factor alpha and interleukin-6 production by human mononuclear phagocytes from allergic asthmatics after IgE-dependent stimulation. American Review of Respiratory Disease, 146, 768–774.

    CAS  PubMed  Google Scholar 

  64. 64.

    Barrios, R. J., Kheradmand, F., Batts, L., & Corry, D. B. (2006). Asthma: Pathology and pathophysiology. Archives of Pathology and Laboratory Medicine, 130, 447–451.

    PubMed  Google Scholar 

  65. 65.

    Wills-Karp, M. (1999). Immunologic basis of antigen-induced airway hyperresponsiveness. Annual Review of Immunology, 18, 17, 255–281.

    Article  CAS  PubMed  Google Scholar 

  66. 66.

    Rothenberg, M. E., Owen, W. F., Jr., Silberstein, D. S., Woods, J., Soberman, R. J., Austen, K. F., et al. (1988). Human eosinophils have prolonged survival, enhanced functional properties, and become hypodense when exposed to human interleukin 3. Journal of Clinical Investigation, 81, 1986–1992.

    CAS  PubMed  Article  Google Scholar 

  67. 67.

    Schon, M. P., & Boehncke, W. H. (2005). Psoriasis. New England Journal of Medicine, 352, 1899–1912.

    Article  CAS  PubMed  Google Scholar 

  68. 68.

    Trembath, R. C., Clough, R. L., Rosbotham, J. L., Jones, A. B., Camp, R. D., Frodsham, A., et al. (1997). Identification of a major susceptibility locus on chromosome 6p and evidence for further disease loci revealed by a two stage genome-wide search in psoriasis. Human Molecular Genetics, 6, 813–820.

    Article  CAS  PubMed  Google Scholar 

  69. 69.

    Griffiths, C. E., Voorhees, J. J., & Nickoloff, B. J. (1989). Characterization of intercellular adhesion molecule-1 and HLA-DR expression in normal and inflamed skin: Modulation by recombinant gamma interferon and tumor necrosis factor. Journal of the American Academy of Dermatology, 20, 617–629.

    CAS  PubMed  Article  Google Scholar 

  70. 70.

    Griffiths, C. E., Voorhees, J. J., & Nickoloff, B. J. (1989). Gamma interferon induces different keratinocyte cellular patterns of expression of HLA-DR and DQ and intercellular adhesion molecule-I (ICAM-I) antigens. British Journal of Dermatology, 120, 1–8.

    Article  CAS  PubMed  Google Scholar 

  71. 71.

    Terui, T., Ozawa, M., & Tagami, H. (2000). Role of neutrophils in induction of acute inflammation in T-cell-mediated immune dermatosis, psoriasis: A neutrophil-associated inflammation-boosting loop. Experimental Dermatology, 9, 1–10.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Sriram Krishnamoorthy.

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Krishnamoorthy, S., Honn, K.V. Inflammation and disease progression. Cancer Metastasis Rev 25, 481–491 (2006).

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  • Inflammation
  • Cancer
  • Atherosclerosis
  • Asthma
  • Psoriasis