Dr David McGrath

Spine Physician

MB BS (Hons) FAFOM, RACP, FAFMM
Master of Pain Medicine

Cytokines (Local Hormones)

1. Soluble GLYCOPROTEINS
2. Secreted by a specific cell type
3. Act on specific cell types
4. Generally short range (paracrine or autocrine )
5. Act on high affinity cell surface receptors
6. Regulate the transcription of cellular genes (up/down) to new cell behaviour
7. Some cytokines may "escape" into wider environment and have systemic actions

8. Activities are tightly regulated. They control local tissue homeostasis.

9. Act in concert, with a "regulation pattern"
10. Immunology is the best studied field, followed by haematology,cell biology in general and oncology

CELL ORIGIN	TYPE	INDIVIDUAL	CELL TARGET
T Helper Lymphocytes (Macrophages, Monocytes)	Lymphokines (Monokines)	MAF (Macrophage Activating) MMIF(Migration Inhibition) MCF (Chemotactic) LMIF (Migration Inhibition) HRF (Histamine Releasing)	Immunology
UNIFIED APPROACH	Interleukins (inter-white cells)	IL1 IL2 IL3 IL4 IL5 IL6	Liver Unified
Immunological Cells	Tumour Necrosis Factors	TNF-alpha (Cachectin) TNF-beta (Lymphotoxin)	Liver
	Interferons	IFN-alpha, IFN-gamma...	Immunology

	Colony Stimulating Factors	G-CSF (Granulocyte) GM-CSF (Granulocyte-macrophage) M-CSF (Macrophage) Multi-CSF (IL-3)	Haematology
	Polypeptide Growth Factors	aFGF (acid Fibroblast ) b FGF (base Fibroblast) EGF (Epidermal) NGF (Nerve) PDGF (Platelet ) VEGF (Vascular Endothelial)	Cell Bilogy
	Transforming Growth Factors	TGF-alpha TGF-beta	Oncology

	Alpha Chemokines	IL-8 NAP-2 (Neutrophil-Activating Protein) PF-4 (Platelet Factor) Beta TG (Thromboglobulin)	Immunology
	Beta Chemokines	MCP-1 (Monocyte Chemotactic) MCP-3 MIP-1 alpha (Macrophage Inflammatory Protein) MIP 1 beta RANTES	Immunology

	Stress Proteins	HSPs (Heat Shock Proteins) GRP's (Glucose Regulated) Ubiquitin SOD(Mn)	Cell Biology

Important Relationships
1. IL1-1 and TNF-alpha stimulate acute phase proteins from liver, and Cortisol from adrenal cortex (via pituitary and ACTH ),which also stimulates acute phase proteins. Cortisol also inhibits IL-1 acting as negative feedback on the local immune reaction, reducing cytokine synthesis. The liver in essence, exerts central control of the inflammatory response away from the local tissue. (The liver is a chemical integration centre) There is a possible connection with stress, which also induces cortisol. Stress, through this mechanism could reduce local inflammation,pehaps interfering with healing. Stress might also be identified through an increase or continuing acute phase response of the liver. (ESR and CRP increases)