Classic signs of inflammation include pain, redness, warmth, and swelling. Healthy inflammation is crucial for the body’s natural defenses against invaders (bacteria, viruses, etc), removal of unhealthy cells (cancer), and facilitating recovery from injury. However, chronic inflammation creates an unhealthy scenario, in which the body’s immune system unnecessarily attacks and destroys healthy tissue and normal cells. Chronic inflammation has been linked to:
- Osteoporosis (weak bones)
- Arthritis (joint disease)
- Sarcopenia (muscle loss and weakness)
- Tendinopathy (chronic tendon injury)
- Atherosclerosis (heart and blood vessel disease)
- Dementia (brain degeneration)
- Some forms of cancer
Inflammation involves a complex interplay and cross-talk between immune cells and injured and/or infected tissue. The precise details of the inflammatory pathway are beyond the scope of this discussion, but it is important to have a basic understanding of inflammation’s main players to help you better understand how sound nutrition and smart training can counteract chronic inflammation’s negative effects.
Inflammation Basics
Inflammation is initiated when immune cells identify invaders (bacteria, viruses, etc), non-viable cells, or injured structures. This causes a migration of immune cells to the target area. Immune cells induce biologic and cellular processes to eradicate germs, completely break down injured cells, and remove the residual waste products.
Ideally, the body completes this phase in a timely and efficient manner, moving on to regeneration and growth as soon as possible. Unfortunately, the immune system sometimes gets bogged down in the early phases of inflammation and never advances to complete rejuvenation.
It is like having a scab that is healing but keeps getting torn off over and over again. Stuck, inflammation becomes self-sustaining and fuels a perpetually downward spiral called chronic inflammation.
Key Immune Cells
T-cells
Primarily produced in the thymus. T-cells contain receptors on their surface that allow them to identify whether or not cells are infected, cancerous, or damaged. Broadly speaking, there are two types of T-cells: Killer T-cells & Helper T-cells.
- Killer T-cells hunt down and destroy cells that are infected with germs or that have become cancerous.
- Helper T-cells coordinate an immune response and play a key role in chronic inflammation and musculoskeletal disease.
B-cells
Primarily produced in the bone marrow. B-cells are responsible for the synthesis of antibodies. Antibodies attach to germs, infected cells, and damaged cells to mark them for disposal. Additionally, research suggests B-cells are a significant source of the signaling protein OPG. OPG reduces the activity and production of bone-resorbing cells (osteoclasts) and promotes new bone formation.
Macrophages
First-line defenders that are able to communicate to T-cells that cells are damaged, infected, or cancerous. Macrophages present information (called an antigen) to the surface of the T-cell. This, combined with macrophage release of special signaling proteins (cytokines), initiates and magnifies the inflammatory process.
Neutrophils
Engulf injured/infected cells and release potent oxygen free radicals (reactive oxygen species) that break down and dispose of injured and infected tissue. As we age, neutrophils become less efficient and cause more collateral damage to healthy tissue.
Cytokines
Cytokines are proteins that act as messengers. Cytokines are similar to hormones, but they are produced by many different cells in many different places and only act locally; not traveling very far from where they are produced.
Cytokines can be produced by all immune cells and tissue-specific cells such as bone cells (osteoblasts & osteoclasts), cartilage cells (chondrocytes), muscle cells (myocytes), and tendon cells (tenocytes).
Most cytokines help coordinate inflammation and instruct individual cells to produce substances that boost inflammation and cause tissue destruction. Important cytokine examples are:
- IL-1β
- TNF-α
- IL-6
Inflammation Intracellular Pathways
Information about the inflammatory process occurring outside the cell must be communicated to key machinery inside the cell, like DNA and mitochondria (the cell’s power generator).
Transmission of information is accomplished via an intricate pathway of surface receptors and intracellular proteins. Inflammation-promoting cytokines activate receptors on the surface of the cell, which in turn activate proteins inside the cell and direct a cascade of events that result in:
- Activation of genes that code for pro-inflammatory enzymes and cytokines (COX-2, iNO2, TNF-α, IL-6)
- Increased production of free radicals (nitric oxide (NO), reactive oxygen species (ROS))
- Increased synthesis of tissue-destroying enzymes (matrix metalloproteinases (MMP))
- Increased production of pro-inflammatory mediators like prostaglandins (PGE2)
- Programmed cell death (apoptosis)
Common intracellular pathways include: MAPK and NF-kB.
Arachidonic Acid Metabolism
Arachidonic acid is a type of omega-6 fat that is stored in cell walls. During inflammation, arachidonic acid is released from the cell wall and converted to a new substance called prostaglandins.
Prostaglandins cause pain, stiffness, and swelling. Pain medications like NSAIDs try to block the conversion of arachidonic acid to prostaglandin by disrupting the COX-2 enzyme.
Osteoarthritis
Osteoarthritis is a disease characterized by structural changes in the joint associated with pain, impaired mobility, and weakness. On a cellular level, osteoarthritis features cartilage degeneration, disorganized architecture, and mitochondrial dysfunction.
Inflammation is a prime driver of joint degeneration, and when exacerbated by excess belly fat, inflammation becomes a potent destructive force that leads to premature joint aging and rapid joint deterioration. Research suggests:
- Belly fat is positively associated both with knee pain and knee cartilage loss.
- The strong synergistic relationship between belly fat and pro-inflammatory cytokines enhances the expression of pro-inflammatory enzymes (iNO2, COX-2) and prostaglandin E2 (PGE2).
- Pro-inflammatory cytokines induce the release of cartilage-eating enzymes (MMPs) and inhibit the synthesis of cartilage components such as proteoglycan and type II collagen.
Osteoporosis
Bone is an active tissue that is constantly being broken down and rebuilt. Osteoporosis can be thought of as a scenario in which bone breakdown outpaces bone regrowth. This mismatch causes overall bone weakness and increases the risk for broken bones, especially in the hips, low back, and wrists.
Chronic inflammation is a risk factor for osteoporosis. Activated T-cells, macrophages, and B-cells release cytokines that, in general, increase the activity of bone-resorbing cells (osteoclasts) and decrease the activity of bone-producing cells (osteoblasts). Some important cytokines are:
- RANKL
- TNF-α
- IL-6
- IL-1
Sarcopenia
Sarcopenia is a disease characterized by decreased muscle synthesis and increased muscle degradation that leads to a loss of muscle mass, weakness, and disability. Research suggests chronic inflammation hastens sarcopenia. Both pro-inflammatory cytokines TNF-α and IL-6 have been associated with:
- Increased muscle breakdown
- Increased insulin resistance that inhibits muscle growth
- Induction of the hormone cortisol that causes severe muscle loss
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